Journal: International journal of molecular sciences

Article Title: Dual Role of Interleukin-20 in Different Stages of Osteoclast Differentiation and Its Osteoimmune Regulation during Alveolar Bone Remodeling.

doi: 10.3390/ijms24043810

Figure Lengend Snippet: Figure 1. IL-20 accelerated OVX-induced bone loss in orthodontic tooth movement by promoting osteoclastogenesis. (A) Scheme illustrating the establishment of orthodontic tooth movement. (B) The distance of orthodontic tooth movement in the Control group, Force group, and OVX + Force group on day 16. (C) TRAP and Immunohistochemical staining showed that TRAP and IL-20 -positive cells and in the Control group, Force group, and OVX + Force group. Green triangles showed TRAP- positive osteoclasts. Red triangles showed IL-20-positive cells. T: tooth, PL: periodontal ligament, AB: alveolar bone. (D) The quantification of TRAP-positive osteoclasts in the Control group, Force group, and OVX + Force group. (E) Immunohistochemical staining and semiquantification of IL-20 in the Control group, Force group, and OVX + Force group. (F) Double-labelled immunofluorescence staining showed that, in the context of orthodontic force, the expression levels of IL-20 and osteoclast marker protein TRAP increased in the first molar periodontal ligament. (G) The distance of orthodon- tic tooth movement in the OVX group, OVX + Force group, and OVX + Force + risedronate group on day 16. (H) TRAP and immunohistochemical staining showed that TRAP and IL-20 -positive cells and in the OVX group, OVX + Force group, and OVX + Force + risedronate group. (I) The quantification of TRAP-positive osteoclasts in the OVX group, ovariectomy + Force group, and Ovariectomy + Force + risedronate group. (J) Immunohistochemical staining and semiquantification of IL-20 in the OVX group, OVX + Force group, and OVX + Force + risedronate group. (K) Im- munofluorescence staining showed that the expression levels of IL-20 and osteoclast marker protein TRAP increased in the first molar periodontal ligament. * p < 0.05 vs. the control group. n = 6.

Article Snippet: After the treatment of IL-20, anti-IL-20 antibody, or TPCA-1 (MCE, Monmouth Junction, NJ, USA), we obtained protein from the samples with cold RIPA containing 1% protease inhibitor cocktail and 1% phosphatase inhibitors.

Techniques: Control, Immunohistochemical staining, Staining, Expressing, Marker

Journal: International journal of molecular sciences

Article Title: Dual Role of Interleukin-20 in Different Stages of Osteoclast Differentiation and Its Osteoimmune Regulation during Alveolar Bone Remodeling.

doi: 10.3390/ijms24043810

Figure Lengend Snippet: Figure 2. IL-20 promoted preosteoclast viability via MAPK pathway at the early stage of osteoclast differentiation. Cell viability was examined in M-CSF-induced preosteoclasts by a CCK8 assay. (A,B) The expression of IL-20 in M-CSF-induced preosteoclasts was determined by cellular im- munofluorescence staining on day 2. (C–F) The mRNA expression levels of IL-20, IL-20RA, IL-20RB, and IL-22RA1 in preosteoclasts were evaluated by qRT-PCR after 2 days of M-CSF treatment. (G) Cell viability detection in preosteoclasts treated with a gradient of concentrations of IL-20 on days 1, 3, 5, and 7. (H) Preosteoclasts were treated with 2 ng/mL IL-20 or anti-IL-20 antibody. The levels of phosphorylation of proteins in the IL-20-mediated signaling pathway, including p38, phos-pho-p38, ERK, phospho-ERK, JNK, and phospho-JNK, were analyzed using Western blotting. IL-20-block group meant that cells were treated with IL-20 and anti-IL-20 antibody. * p < 0.05 vs. the 0 ng/mL IL-20 group. ns p > 0.05 vs. the 0 ng/mL IL-20 group. n = 6.

Article Snippet: After the treatment of IL-20, anti-IL-20 antibody, or TPCA-1 (MCE, Monmouth Junction, NJ, USA), we obtained protein from the samples with cold RIPA containing 1% protease inhibitor cocktail and 1% phosphatase inhibitors.

Techniques: CCK-8 Assay, Expressing, Staining, Quantitative RT-PCR, Phospho-proteomics, Western Blot, Blocking Assay

Journal: International journal of molecular sciences

Article Title: Dual Role of Interleukin-20 in Different Stages of Osteoclast Differentiation and Its Osteoimmune Regulation during Alveolar Bone Remodeling.

doi: 10.3390/ijms24043810

Figure Lengend Snippet: Figure 3. IL-20 had no effect on osteoclast formation at the early stage of osteoclast differentiation. (A) Scheme illustrating bone marrow-derived macrophages were cultured in osteoclast medium containing M-CSF and IL-20 or anti-IL-20 antibody at the early stage of osteoclast differentiation, and then induced with the presence of 10, 30, or 60 ng/mL RANKL. The control group included M-CSF-induced preosteoclasts induced with 10, 30, or 60 ng/mL RANKL. (B) TRAP staining was performed, and the number and size of TRAP-positive osteoclasts with more than three nuclei were quantified on day 6. IL-20-block group meant that cells were treated with IL-20 or anti-IL-20 antibody. (C) A bone resorption pit assay was performed to detect osteoclast function, and bone resorption pits were counted, and the area and number of bone resorption were quantified on day 6. IL-20- block group meant that cells were treated with IL-20 and anti-IL-20 antibody. (D) M-CSF-induced preosteoclasts were cultured in osteoclast medium containing different concentrations of IL-20 or anti-IL-20 antibody without RANKL. n = 6.

Article Snippet: After the treatment of IL-20, anti-IL-20 antibody, or TPCA-1 (MCE, Monmouth Junction, NJ, USA), we obtained protein from the samples with cold RIPA containing 1% protease inhibitor cocktail and 1% phosphatase inhibitors.

Techniques: Derivative Assay, Cell Culture, Control, Staining, Blocking Assay

Journal: International journal of molecular sciences

Article Title: Dual Role of Interleukin-20 in Different Stages of Osteoclast Differentiation and Its Osteoimmune Regulation during Alveolar Bone Remodeling.

doi: 10.3390/ijms24043810

Figure Lengend Snippet: Figure 4. IL-20 promoted RANKL-induced osteoclast differentiation and bone resorption function. (A) Scheme illustrating M-CSF-induced preosteoclasts were cultured in osteoclast medium containing IL-20 or anti-IL-20 antibody at the late stage of osteoclast differentiation in the presence of 10, 30, or 60 ng/mL RANKL. (B) TRAP staining was performed, and the number and size of TRAP-positive osteoclasts with more than three nuclei were quantified at the late stage of differentiation on day 6. The control group included M-CSF-induced preosteoclasts induced with 10, 30, or 60 ng/mL RANKL. IL-20-block group meant that cells were treated with IL-20 and anti-IL-20 antibody. (C) A resorption pit assay was performed to detect osteoclast function, and resorption pits were counted at the late stage of differentiation on day 6, and the area and number of bone resorption were quantified at the stage of differentiation. IL-20-block group meant that cells were treated with IL-20 and anti-IL-20 antibody. * p < 0.05 vs. the control group. n = 6.

Article Snippet: After the treatment of IL-20, anti-IL-20 antibody, or TPCA-1 (MCE, Monmouth Junction, NJ, USA), we obtained protein from the samples with cold RIPA containing 1% protease inhibitor cocktail and 1% phosphatase inhibitors.

Techniques: Cell Culture, Staining, Control, Blocking Assay

Journal: International journal of molecular sciences

Article Title: Dual Role of Interleukin-20 in Different Stages of Osteoclast Differentiation and Its Osteoimmune Regulation during Alveolar Bone Remodeling.

doi: 10.3390/ijms24043810

Figure Lengend Snippet: Figure 5. IL-20 promoted the expression of osteoclast-specific genes and proteins via NF-κB pathway during RANKL-induced osteoclast differentiation. Preosteoclasts were stimulated with IL-20 or NF-κB pathway inhibitor TPCA-1. (A,B) IL-20 promoted phospho-P65 nuclear translocation and was blocked by TPCA-1 in preosteoclasts after 1 h treatment, with or without RANKL. (C) The levels of phosphorylation for proteins in the NF-κB pathway, including the IKKα/β, IκB-α, and P65 proteins in preosteoclasts were detected using Western blotting. (D) The levels of activated proteins in preosteoclasts, including the RANK, TRAF6, c-Fos, and NFATc1 proteins without RANKL were detected using Western blotting. (E) The protein expression levels of TRAP, Cathepsin K, RANK, TRAF6, c-Fos and NFATc1 in osteoclasts were examined using Western blotting after 6 days of IL-20 treatment. (F–K) The mRNA expression levels of TRAP, Cathepsin K, MMP9, MT1-MMP, c-Fos, and NFATc1 in osteoclasts were detected by qRT-PCR after 6 days of IL-20 treatment. * p < 0.05 vs. the 0 ng/mL IL-20 group. n = 6.

Article Snippet: After the treatment of IL-20, anti-IL-20 antibody, or TPCA-1 (MCE, Monmouth Junction, NJ, USA), we obtained protein from the samples with cold RIPA containing 1% protease inhibitor cocktail and 1% phosphatase inhibitors.

Techniques: Expressing, Translocation Assay, Phospho-proteomics, Western Blot, Quantitative RT-PCR

Journal: International journal of molecular sciences

Article Title: Dual Role of Interleukin-20 in Different Stages of Osteoclast Differentiation and Its Osteoimmune Regulation during Alveolar Bone Remodeling.

doi: 10.3390/ijms24043810

Figure Lengend Snippet: Figure 6. Therapeutic effect of IL-20 on orthodontic tooth movement. (A,B) Micro-CT showed the distance of orthodontic tooth movement between first and second molars treated with local infusion of IL-20 or an-ti-IL-20 antibody, seven days after the application of orthodontic force. OTM + IL- 20-block group meant that rats were locally infused with anti-IL-20 antibody. (C,D) TRAP staining and the quantification of TRAP-positive osteoclasts in the OTM group, OTM + IL-20 group, and OTM + anti-IL-20 antibody group. Green triangles showed TRAP-positive osteoclasts. OTM + IL-20- block group meant that rats were locally infused with anti-IL-20 antibody. (E,F) Immunofluorescence staining showed that the expression levels of osteoclast marker protein RANK in the first molar periodontal ligament after the application of orthodontic force. OTM + IL-20-block group meant that rats were locally infused with anti-IL-20 antibody. (G,H) Immunofluorescence staining showed that the expression levels of MCP-1 and CD11b in the first molar periodontal ligament after the application of orthodontic force. * p < 0.05 vs. the control group. n = 6.

Article Snippet: After the treatment of IL-20, anti-IL-20 antibody, or TPCA-1 (MCE, Monmouth Junction, NJ, USA), we obtained protein from the samples with cold RIPA containing 1% protease inhibitor cocktail and 1% phosphatase inhibitors.

Techniques: Micro-CT, Blocking Assay, Staining, Expressing, Marker, Control

Journal: Cell Communication and Signaling : CCS

Article Title: Interleukin-22 receptor 1-mediated stimulation of T-type Ca 2+ channels enhances sensory neuronal excitability through the tyrosine-protein kinase Lyn-dependent PKA pathway

doi: 10.1186/s12964-024-01688-6

Figure Lengend Snippet: IL-24 enhances T-currents in small-sized TG neurons. ( A ) The left panel shows representative traces, and the right panel provides a summary data, indicating the inhibition of T-currents by Ni 2+ (50 µM) ( n = 8 cells). *** p < 0.001 (compared to control, paired t-test). ( B ) Summary data revealing the effect of TTA-P2 (3 µM) on T-currents in TG neurons ( n = 7 cells). *** p < 0.001 (compared to control, paired t-test). ( C ) Time course of current changes ( left panel ) and summary data ( right panel ) demonstrate the enhancement of T-currents induced by 150 ng/ml IL-24 ( n = 10 cells). *** p < 0.001 (compared to control, paired t-test). # p < 0.05 (compared to IL-24, paired t -test). ( D ) A dose-response curve of IL-24 on T-currents is depicted, with the solid line representing the best fit using the Hill equation. The number of cells recorded at each IL-24 dose is displayed in round brackets. ( E ) The current-voltage curve displays the increased T-current density induced by 150 ng/ml IL-24 ( n = 12 cells). * p < 0.05 (compared to control, one-way ANOVA). ( F-G ) IL-24 at 150 ng/ml did not alter the voltage-dependent activation properties of T-type channels ( F , n = 12 cells) but shifted steady-state inactivation properties in a depolarizing direction ( G , n = 12 cells). Insets , simulation waveforms. ( H ) Summary of results of V half . *** p < 0.001 (compared to control, one-way ANOVA)

Article Snippet: IL-24, Rp-cAMPs, and SB203580 were obtained from MedChemExpress.

Techniques: Inhibition, Control, Activation Assay

Journal: Cell Communication and Signaling : CCS

Article Title: Interleukin-22 receptor 1-mediated stimulation of T-type Ca 2+ channels enhances sensory neuronal excitability through the tyrosine-protein kinase Lyn-dependent PKA pathway

doi: 10.1186/s12964-024-01688-6

Figure Lengend Snippet: IL-22R1 mediates the IL-24-induced increase in T-currents. ( A-B ) Immunoblot analysis of IL-20R1 ( A ) and IL-22R1 ( B ) in the spinal cord (SC) and TG of intact mice. Representative blots from at least 3 independent experiments are displayed. ( C-D ) Protein abundance of IL-20R1 ( C ) or IL-22R1 ( D ) in TG cells treated with IL-20R1 siRNA (IL-20R1-siRNA) or IL-22R1-siRNA. NC-siRNA, negative control siRNA. ** p < 0.01 and *** p < 0.001 (compared to NC-siRNA, unpaired t- test). Representative blots from at least 3 independent experiments are displayed. ( E-F ) Representative traces ( left ) and summary data ( right ) indicating that treatment of IL-22R1-siRNA ( n = 9 cells), but not IL-20R1-siRNA ( n = 9 cells), prevented the IL-24-induced T-current increase. IL-24 at 150 ng/ml significantly enhanced T-currents in TG cells transduced with NC-siRNA in panels E ( n = 9 cells) and F ( n = 9 cells), respectively. ** p < 0.01 and *** p < 0.001 (compared to control, unpaired t- test). ( G ) Colocalization of IL-22R1 ( red ) with NeuN, GS, CGRP, IB 4 or NF200 ( green ) in TG sections of intact mice. White arrows indicate colocalization. Scale bar, 50 μm

Article Snippet: IL-24, Rp-cAMPs, and SB203580 were obtained from MedChemExpress.

Techniques: Western Blot, Quantitative Proteomics, Negative Control, Transduction, Control

Journal: Cell Communication and Signaling : CCS

Article Title: Interleukin-22 receptor 1-mediated stimulation of T-type Ca 2+ channels enhances sensory neuronal excitability through the tyrosine-protein kinase Lyn-dependent PKA pathway

doi: 10.1186/s12964-024-01688-6

Figure Lengend Snippet: The IL-22R1-induced T-current response required the protein kinase Lyn. ( A ) The protein abundance of phosphorylated JAK1 ( p -JAK1) or total JAK1 ( t -JAK1) in TG cells treated with 150 ng/ml IL-24. Representative blots from at least 3 independent experiments are displayed. ( B ) The left panel shows representative traces, and the right panel provides a summary data, indicating the effect of IL-24 (150 ng/ml) on T-currents in cells pretreated with GPLG0634 (1 µM) ( n = 7 cells). Letters ( a and b ) denote the points used for exemplary current traces. *** p < 0.001 (compared to control, paired t- test). ( C ) IL-24 increased the protein levels of phosphorylated p38 ( p -p38), with no significant changes in p -ERK and p -JNK. Representative blots from at least 3 independent experiments are displayed. *** p < 0.001 (compared to control, unpaired t- test). ( D ) The left panel shows representative traces, and the right panel provides a summary data, indicating the effect of IL-24 (150 ng/ml) on T-currents in cells pretreated with SB203580 (10 µM) ( n = 8 cells). Letters ( a and b ) denote the points used for exemplary current traces. *** p < 0.001 (compared to control, paired t- test). ( E ) Immunoblot analysis of p -Lyn or t -Lyn in TG cells treated with 150 ng/ml IL-24. Representative blots from at least 3 independent experiments are displayed. *** p < 0.001 (compared to control, paired t- test). ( F ) The left panel shows representative traces, and the right panel provides a summary data, indicating the effect of IL-24 (150 ng/ml) on T-currents in cells pretreated with bafetinib (1 µM) ( n = 8 cells). Letters ( a and b ) represent points used for exemplary current traces. ( G ) Protein abundance of Lyn in TG cells treated with Lyn-siRNA. *** p < 0.001 (compared to NC-siRNA, unpaired t- test). Representative blots from at least 3 independent experiments are displayed. ( H ) Representative traces and bar graph indicating that treatment of Lyn-siRNA ( n = 10 cells), but not NC-siRNA ( n = 9 cells), prevented the IL-24-induced T-current increase. IL-24 at 150 ng/ml significantly enhanced T-currents in TG cells transduced with NC-siRNA in panel H ( n = 9 cells). *** p < 0.001 (compared to control, unpaired t- test)

Article Snippet: IL-24, Rp-cAMPs, and SB203580 were obtained from MedChemExpress.

Techniques: Quantitative Proteomics, Control, Western Blot, Transduction

Journal: Cell Communication and Signaling : CCS

Article Title: Interleukin-22 receptor 1-mediated stimulation of T-type Ca 2+ channels enhances sensory neuronal excitability through the tyrosine-protein kinase Lyn-dependent PKA pathway

doi: 10.1186/s12964-024-01688-6

Figure Lengend Snippet: PKA is involved in the IL-24-mediated T-current response. ( A-B ) Time course of T-current changes demonstrating the effect of IL-24 (150 ng/ml) on T-currents in TG cells preincubated with 1 µM GF109203X ( A ) or 1 µM Go6976 ( B ), respectively. Letters ( a and b ) represent points used for exemplary current traces. ( C ) Summary of results revealing the effect of IL-24 (150 ng/ml) on T-currents in TG neurons pretreated with GF109203X ( n = 8 cells) or Go6976 ( n = 7 cells). ( D ) Protein expression of phosphorylated PKA ( p -PKA, PKA activation) in TG cells induced by IL-24 (150 ng/ml) in the presence or absence of bafetinib (1 µM). Representative blots from at least 3 independent experiments are displayed. ** p < 0.01 (compared to control, unpaired t- test). ( E ) Application of forskolin (20 µM), but not IL-24 (150 ng/ml), increased cAMP contents in TG cells. *** p < 0.001 (compared to control, unpaired t- test). ( F-G ) Time course of T-current changes demonstrating the effect of IL-24 (150 ng/ml) on T-currents in TG neurons pretreated with Rp-cAMPs (10 µM) ( F ) or dialyzed with PKI 6–22 (5 µM) ( G ), respectively. Letters ( a and b ) denote the points used for exemplary current traces. ( H ) Bar graph showing the effect of 150 ng/ml IL-24 on T-currents in cells pretreated with Rp-cAMPs ( n = 8 cells) or dialyzed with PKI 6–22 ( n = 7 cells). ** p < 0.01 (compared to control, unpaired t -test)

Article Snippet: IL-24, Rp-cAMPs, and SB203580 were obtained from MedChemExpress.

Techniques: Expressing, Activation Assay, Control

Journal: Cell Communication and Signaling : CCS

Article Title: Interleukin-22 receptor 1-mediated stimulation of T-type Ca 2+ channels enhances sensory neuronal excitability through the tyrosine-protein kinase Lyn-dependent PKA pathway

doi: 10.1186/s12964-024-01688-6

Figure Lengend Snippet: IL-24 induces TG neuronal hyperexcitability. ( A-C ) Representative traces ( left ) and summary of results ( right ) demonstrating the effect of IL-24 (150 ng/ml) on Nav currents ( A , I Na , n = 9 cells), high-voltage activated (HVA) Ca 2+ currents ( B , n = 9 cells), transient outward K + channel currents ( I A , upper panel ) ( C , n = 9 cells), or sustained delayed-rectifier K + currents ( I DR , lower panel ) ( C , n = 9 cells). I Na was elicited from the holding potential of -90 mV and depolarized to -10 mV. HVA Ca 2+ currents were elicited from the holding potential of -60 mV and depolarized to 0 mV. Kv currents are depolarized from a holding potential of -80 mV to + 40 mV. To obtain I A , a 150 msec prepulse to -10 mV was included to inactivate the transient channels, resulting in sustained I DR isolation. Offline subtraction of I DR from the total current yielded I A. * p < 0.05 (compared to control, paired t- test). ( D-E ) Representative traces ( D ) and summary of results ( E ) demonstrating that IL-24 at 150 ng/ml significantly increased the action potential (AP) firing rate ( n = 12 cells). Insets indicate the protocols of current injection. *** p < 0.001 (compared to control, paired t- test). # p < 0.05 (compared to IL-24, paired t-test). ( F-G ) Effect of 150 ng/ml IL-24 on the rheobase ( F ) and resting membrane potential (RMP) ( G ) of AP firing ( n = 12 cells). * p < 0.05 (compared to control, paired t- test). ( H ) Bar graph revealing that pretreatment of TG neurons with bafetinib (1 µM, n = 11 cells) or dialyzed with PKI 6–22 (5 µM, n = 11 cells) completely abolished the increased AP firing rate induced by IL-24. ( I ) The left panel shows representative traces, and the right panel provides a summary data, indicating that application of Ni 2+ at 50 µM abrogated the increased AP firing rate induced by IL-24 ( n = 10 cells). ( J ) Summary of results revealing that Cav3.2-siRNA ( n = 9 cells), but not its NC-siRNA ( n = 10 cells), prevented the 150 ng/ml IL-24-induced increase in AP firing rate. *** p < 0.001 (compared to control + NC-siRNA, unpaired t- test)

Article Snippet: IL-24, Rp-cAMPs, and SB203580 were obtained from MedChemExpress.

Techniques: Isolation, Control, Injection, Membrane

Journal: Cell Communication and Signaling : CCS

Article Title: Interleukin-22 receptor 1-mediated stimulation of T-type Ca 2+ channels enhances sensory neuronal excitability through the tyrosine-protein kinase Lyn-dependent PKA pathway

doi: 10.1186/s12964-024-01688-6

Figure Lengend Snippet: Peripheral IL-24/IL-22R1 induces mechanical pain hypersensitivity. ( A ) Escape threshold after intra-TG administration of 100 ng IL-24 or vehicle. * p < 0.05 and *** p < 0.001 (compared to vehicle, two-way ANOVA). BL, baseline. ( B-C ) Effects of IL-22R1-siRNA ( B ) or IL-20R1-siRNA ( C ) as well as the corresponding control siRNAs (NC-siRNAs) on IL-24 (100 ng, intra-TG injection; arrow)-induced mechanical hypersensitivity. ** p < 0.05 (compared to NC-siRNA at 1 h) and # p < 0.05 (compared to NC-siRNA at 0 h) (two-way ANOVA). ( D ) Pretreatment with TTA-P2 (1 nmol) attenuated 100 ng IL-24-induced mechanical hypersensitivity. * p < 0.05 and *** p < 0.001 (compared to IL-24 at 1 h), # p < 0.05 (compared to vehicle + TTA-P2) (two-way ANOVA). ( E ) Escape threshold to mechanical stimuli in the sham- or CCI-ION-operated mice. * p < 0.05 and *** p < 0.001 (compared to sham, two-way ANOVA). ( F ) Immunoblot analysis of IL-22R1 in TGs on day 14 after CCI-ION-operation or sham surgery. ** p < 0.01 (compared to sham, unpaired t- test). Representative blots from at least 3 independent experiments are displayed. ( G ) Intra-TG injection of IL-22R1-siRNA 14 days after CCI-ION alleviated mechanical pain hypersensitivity in CCI-ION mice. * p < 0.05 (compared to NC-siRNA at the corresponding time point, two-way ANOVA). ( H ) The effect of Cav3.2-siRNA versus NC-siRNA (Day 0) on IL-22R1-siRNA (Day 3)-induced alleviation of mechanical allodynia in CCI-ION mice. *** p < 0.001 (compared to CCI-ION at -14 days), + p < 0.05 and ++ p < 0.01 (compared to NC-siRNA at the 3-day point in CCI-ION mice), ## p < 0.01 (compared to Cav3.2-siRNA at the 0-day point in CCI-ION mice) (two-way ANOVA). For all animal behavior detection, N = 7–9 mice for each group

Article Snippet: IL-24, Rp-cAMPs, and SB203580 were obtained from MedChemExpress.

Techniques: Control, Injection, Western Blot

Journal: Cell Communication and Signaling : CCS

Article Title: Interleukin-22 receptor 1-mediated stimulation of T-type Ca 2+ channels enhances sensory neuronal excitability through the tyrosine-protein kinase Lyn-dependent PKA pathway

doi: 10.1186/s12964-024-01688-6

Figure Lengend Snippet: The proposed mechanisms of IL-22R1 signaling on T-type channels. IL-24 engages IL-22R1, leading to the activation of tyrosine protein kinase Lyn. Lyn then stimulates downstream cAMP-independent PKA, which in turn modulates the activity of T-type channels, resulting in an increase in T-currents. This signaling cascade mediated by IL-22R1 contributes to the hyperexcitability of trigeminal ganglion (TG) neurons and the nociceptive behaviors induced by IL-24. Notably, IL-22R1 is upregulated in the injured TG, and blocking Cav3.2 attenuates IL-22R1-mediated pain hypersensitivity in neuropathic pain behaviors induced by CCI-ION. JAK1, MAPK, and PKC do not appear to be involved in the IL-24-mediated response of T-currents. Created by Biorender.com

Article Snippet: IL-24, Rp-cAMPs, and SB203580 were obtained from MedChemExpress.

Techniques: Activation Assay, Activity Assay, Blocking Assay