p38 mapk inhibitor sb203580  (MedChemExpress)

Journal: bioRxiv

Article Title: An APP-centered molecular gateway integrates innate immunity and retinoic acid signaling to drive irreversible metamorphic commitment

doi: 10.64898/2026.01.22.700939

Figure Lengend Snippet: (A) Settlement rate of inhibitor-treated larvae. The box plots with superimposed jitter plots display the larval settlement rate under various inhibitor treatments. The biofilm stimulus condition is used as the positive control. The concentration of each inhibitor is indicated on the horizontal axis. The data represent the settlement rate of larvae remaining attached out of 10 larvae across six independent biological replicates (total n = 60). Statistical significance among treatment groups was assessed using one-way ANOVA followed by Tukey’s HSD post hoc test, with grouping letters indicating significant differences ( p < 0.05); treatments sharing a letter are not significantly different. (B) Quantitative assessment of the functional hierarchy. The box plots with superimposed jitter plots show the Metamorphic Progression Scores (MPS) for larvae treated with various pharmacological inhibitors with or without all-trans retinoic acid (RA). The MPS was calculated based on the metamorphic stage reached by the larvae in the identical assays used for the settlement rate analysis in (A). The concentration of each inhibitor is indicated on the horizontal axis. The MPS represents the average metamorphic stage reached (0 = brachiolaria; 1 = early; 2 = middle; 3 = late; 4 = pre-juvenile; 5 = juvenile). Statistical significance among the treatment groups was assessed using one-way ANOVA followed by Tukey’s HSD post hoc test ( *p < 0.05; n.s., not significant). A significant RA-dependent rescue condition (a statistically significant increase in MPS compared with the inhibitor-alone condition) is highlighted in grey, establishing the functional hierarchy of the pathways relative to the RA commitment signal. (C) Representative image illustrating pathway functional hierarchy. Images show representative larval morphology under the control, inhibitor-only, and inhibitor + RA conditions. These images specifically represent the high-concentration inhibitor treatments (MyD88 inhibitor: 50 µM; MAPK inhibitors: 10 µM; IKKβ and HSP90AA1 inhibitors: 1 µM). MyD88 inhibition completely blocks the behavioral decision of settlement. JNK and p38 inhibition caused a distinct early-stage arrest (low MPS), and the effects of their inhibition were significantly rescued by RA co-treatment. In contrast, ERK inhibition arrested metamorphosis at the middle stage, and this block was not rescued by exogenous RA. Similarly, IKKβ and HSP90AA1 inhibition arrested metamorphosis at later stages, and this block was not rescued by exogenous RA, functionally placing all three pathways (ERK, IKKβ, and HSP90AA1) downstream of the RA commitment signal. Scale bar: 200 µm. Inhibitors used: T6167923 (MyD88 inhibitor), IKK-16 (IKKβ inhibitor), U0126 (ERK inhibitor), SP600125 (JNK inhibitor), SB202190 (p38 inhibitor), and Luminespib (HSP90AA1 inhibitor).

Article Snippet: The inhibitors were dissolved in DMSO and applied at the indicated concentrations: the MyD88 inhibitor T6167923 (5 or 50 μM; MedChemExpress), the IKKβ inhibitor IKK-16 (0.1 or 1 μM; MedChemExpress), and MAPK inhibitors SP600125 (JNK), SB202190 (p38), and U0126 (ERK) (1 or 10 μM; MedChemExpress or FUJIFILM Wako Pure Chemical Corporation), and the HSP90AA1 inhibitors luminespib (0.1 or 1 μM; Chemscene).

Techniques: Positive Control, Concentration Assay, Functional Assay, Control, Inhibition, Blocking Assay

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Liver Sinusoidal Endothelial Cells Promote Metabolic Dysfunction-associated Steatohepatitis Progression via Interleukin-1R1-mediated Chemokine Production Induced by Macrophage-derived Interleukin-1β

doi: 10.1016/j.jcmgh.2025.101698

Figure Lengend Snippet: Increased IL-1β secretion by macrophages due to autophagy impairment enhances inflammatory chemokine expression in LSECs. ( A ) Protein expression in ATG7-KO macrophages and NC macrophages generated using the CRISPR-CAS9 system. ( B ) Evaluation of IL-1β and caspase-1 levels in the culture supernatant of THP-1 macrophages by ELISA following 24-hour stimulation with or without 25 ng/mL LPS (n = 3/group). ( C ) Experimental method using LPS-stimulated THP-1 macrophage conditioned medium. ( D ) Evaluation of NF-κB or MAP kinase-related proteins in TMNK-1 cells. ( E and F ) Inflammatory chemokine gene expression in TMNK-1 cells when treated with control medium or THP-1 macrophage conditioned medium (n = 4/group). SN50, NF-κB inhibitor; SP600125, JNK inhibitor; SB203580, p38 MAPK inhibitor. ( G ) Inflammatory chemokine gene expression measured 24 hours after treating TMNK-1 cells with varying concentrations of human recombinant IL-1β (n = 4/group). ( H ) Evaluation of inflammatory chemokine expression in TMNK-1 cells after 6 hours of stimulation with recombinant human IL-1β (5 ng/mL) in the presence of SP600125 and SB203580 (n = 4/group).

Article Snippet: The inhibitors used were as follows: the NF-κB inhibitor SN50 (HY-P0151; MedChemExpress), the JNK inhibitor SP600125 (HY-12041; MedChemExpress), the p38 MAPK inhibitor SB 203580 (HY-10256; MedChemExpress), and the IL-1R antagonist (IL-1Ra) (093-05991; FUJIFILM Wako Pure Chemical Corporation).

Techniques: Expressing, Generated, CRISPR, Enzyme-linked Immunosorbent Assay, Gene Expression, Control, Recombinant

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: Liver Sinusoidal Endothelial Cells Promote Metabolic Dysfunction-associated Steatohepatitis Progression via Interleukin-1R1-mediated Chemokine Production Induced by Macrophage-derived Interleukin-1β

doi: 10.1016/j.jcmgh.2025.101698

Figure Lengend Snippet: Macrophage-derived IL-1β increases CCL2 expression in HSCs via JNK activation. ( A ) Evaluation of the levels of NF-κB or MAPK-related proteins in LX-2 cells. ( B, C ) CCL2 gene expression in LX-2 cells treated with the control medium or THP-1 macrophage conditioned medium (n = 3/group). SN50, NF-κB inhibitor; SP600125, JNK inhibitor; SB203580, p38 MAPK inhibitor. ( D ) Evaluation of CCL2 expression in TMNK-1 cells after 48 hours of stimulation with recombinant human IL-1β (5 ng/mL) in the presence of SP600125 and SB203580 (n = 4/group).

Article Snippet: The inhibitors used were as follows: the NF-κB inhibitor SN50 (HY-P0151; MedChemExpress), the JNK inhibitor SP600125 (HY-12041; MedChemExpress), the p38 MAPK inhibitor SB 203580 (HY-10256; MedChemExpress), and the IL-1R antagonist (IL-1Ra) (093-05991; FUJIFILM Wako Pure Chemical Corporation).

Techniques: Derivative Assay, Expressing, Activation Assay, Gene Expression, Control, Recombinant