p38 map kinase inhibitor sb202190  (Enzo Biochem)

Journal: Arthritis Research & Therapy

Article Title: Cytokine signaling-1 suppressor is inducible by IL-1beta and inhibits the catabolic effects of IL-1beta in chondrocytes: its implication in the paradoxical joint-protective role of IL-1beta

doi: 10.1186/ar4381

Figure Lengend Snippet: Effects of SOCS1 on MAP kinase signaling. SW1353 cells were transfected with SOCS1 or shSOCS1 vectors to overexpress or inhibit SOCS1, as described in Methods. A representative immunoblot image showed that SOCS1 overexpression decreased phosphorylation of p38 and JNK, whereas SOCS1 knockdown increased their phosphorylation in the presence of IL-1β (10 ng/ml, A) . The relative proportions of phosphorylated to total protein were determined with densitometry by using Image J software (version 1.48c, [ 22 ]; B) . Data were expressed as the means ± SEM ( n = 3). OE, overexpression; KD, knockdown.

Article Snippet: A p38 MAP kinase inhibitor SB202190 and NF-κB inhibitor SN50 were purchased from Alexis Biochemicals (Farmingdale, MI, USA).

Techniques: Transfection, Over Expression, Software

Journal: Arthritis Research & Therapy

Article Title: Cytokine signaling-1 suppressor is inducible by IL-1beta and inhibits the catabolic effects of IL-1beta in chondrocytes: its implication in the paradoxical joint-protective role of IL-1beta

doi: 10.1186/ar4381

Figure Lengend Snippet: Effect of MAP kinase and NF-κB inhibitors on MMPs secretion from SOCS1-knockdown SW1353 cells. SOCS1-knockdown SW1353 cells were pretreated with inhibitors for 1 hour before stimulation with 10 ng/ml of IL-1β. After 24 hours, the levels of MMP-1, -3, and -13 were dramatically decreased by SB202190, a p38 MAP kinase inhibitor (A) . Blockade of C-JNK (B) and ERK (C) dose-dependently suppressed the secretion of MMPs from shSOCS1-transfected SW1353 cells. The production of MMP-1 and MMP-13 was partially inhibited with the SN50, a specific NF-κB inhibitory peptide (D) . Data were expressed as the mean ± SEM of relative MMPs levels, as compared with the control without inhibitors ( n = 3). *P

Article Snippet: A p38 MAP kinase inhibitor SB202190 and NF-κB inhibitor SN50 were purchased from Alexis Biochemicals (Farmingdale, MI, USA).

Techniques: Transfection

Journal: The FASEB Journal

Article Title: The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis

doi: 10.1096/fj.13-228858

Figure Lengend Snippet: Proposed mechanisms of PGE 2 production induced by TLR2/p38 MAPK and EP4 stimulation, leading to optimal PGE 2 production and protection against necrosis in Mtb -infected Mφs. PGE 2 generated by TLR2 stimulation/p38 MAPK phosphorylation following

Article Snippet: Phospho-p38 mitogen-activated protein kinase (MAPK; Thr180 /Tyr182 ) antibody, p38 MAPK antibody, glyceraldehyde 3-phosphate dehydrogenase (GAPDH; 14C10) rabbit mAb, and COX1 (D2G6) rabbit mAb were from Cell Signaling Technology (Beverly, MA, USA); p38 MAPK inhibitor SB202190 was from Enzo Life Sciences (Farmingdale, NY, USA).

Techniques: Infection, Generated

Journal: The FASEB Journal

Article Title: The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis

doi: 10.1096/fj.13-228858

Figure Lengend Snippet: Regulation of COX2 and mPGES-1 expression and PGE 2 production by p38 MAPK in H37Ra-infected human Mφs. A ) Western blot of time-dependent p38 MAPK phosphorylation in H37Ra infection (MOI 10:1). Ratio of P-p38 MAPK to p38 MAPK is indicated for every

Article Snippet: Phospho-p38 mitogen-activated protein kinase (MAPK; Thr180 /Tyr182 ) antibody, p38 MAPK antibody, glyceraldehyde 3-phosphate dehydrogenase (GAPDH; 14C10) rabbit mAb, and COX1 (D2G6) rabbit mAb were from Cell Signaling Technology (Beverly, MA, USA); p38 MAPK inhibitor SB202190 was from Enzo Life Sciences (Farmingdale, NY, USA).

Techniques: Expressing, Infection, Western Blot

Journal: The FASEB Journal

Article Title: The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis

doi: 10.1096/fj.13-228858

Figure Lengend Snippet: TLR2 stimulation of human Mφs induces COX2 and mPGES-1 expression through the p38 MAPK and EP4 signaling pathways. A ) Western blot of p38 MAPK phosphorylation at different time points in Mφs treated with TLR1/2 agonist Pam3CSK4 (10 μg/ml)

Article Snippet: Phospho-p38 mitogen-activated protein kinase (MAPK; Thr180 /Tyr182 ) antibody, p38 MAPK antibody, glyceraldehyde 3-phosphate dehydrogenase (GAPDH; 14C10) rabbit mAb, and COX1 (D2G6) rabbit mAb were from Cell Signaling Technology (Beverly, MA, USA); p38 MAPK inhibitor SB202190 was from Enzo Life Sciences (Farmingdale, NY, USA).

Techniques: Expressing, Western Blot

Journal: The FASEB Journal

Article Title: The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis

doi: 10.1096/fj.13-228858

Figure Lengend Snippet: Role of EP4 in the activation of the p38 MAPK signaling in H37Ra-infected human Mφs. A ) Western blot of p38 MAPK phosphorylation in Mφs stimulated with the EP4 agonist ONO-AE1-329 (10 μM). Mφ lysates treated with DMSO (final

Article Snippet: Phospho-p38 mitogen-activated protein kinase (MAPK; Thr180 /Tyr182 ) antibody, p38 MAPK antibody, glyceraldehyde 3-phosphate dehydrogenase (GAPDH; 14C10) rabbit mAb, and COX1 (D2G6) rabbit mAb were from Cell Signaling Technology (Beverly, MA, USA); p38 MAPK inhibitor SB202190 was from Enzo Life Sciences (Farmingdale, NY, USA).

Techniques: Activation Assay, Infection, Western Blot

Journal: Respiratory Research

Article Title: Epithelial cell senescence impairs repair process and exacerbates inflammation after airway injury

doi: 10.1186/1465-9921-12-78

Figure Lengend Snippet: P38 MAPK inhibitor suppresses senescence-associated airway inflammation in mice . ( A ) Representative photomicrographs of double immunofluorescence staining for phospho-p38 MAPK ( green ) and CC10 ( red ) in the distal airway. Arrows indicate CC10-positive Clara cells that express phospho-p38 MAPK in their nuclei. Treatment with SB202190 of mice repeatedly exposed to NA and injected with BrdU reduces the proportion of Clara cells that express phospho-p38 MAPK ( B ) and the numbers of CD45-positive cells and CD90.2-positive cells infiltrating the distal airways ( C ) but does not affect the number of Clara cells ( D ) or the number of Clara cells that express p21 ( E ). Data are expressed as the means ± SEM. N = 4-6 in each experiment.

Article Snippet: The p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190 (Enzo Life Sciences, Plymouth Meeting, PA) or 0.1% DMSO was administered by intraperitoneal injection 30 minutes before each BrdU injection.

Techniques: Mouse Assay, Double Immunofluorescence Staining, Injection

Journal: Respiratory Research

Article Title: Epithelial cell senescence impairs repair process and exacerbates inflammation after airway injury

doi: 10.1186/1465-9921-12-78

Figure Lengend Snippet: P38 MAPK activation in senescent Clara cells in the airways of COPD patients . ( A ) Representative photomicrographs of triple immunofluorescence staining of lung tissue sections obtained from COPD patients. Arrows indicate CC10-positive Clara cells that express both p16 and phospho-p38 MAPK. The arrowhead indicates a CC10-positive cell that expresses p16 but not phospho-p38 MAPK ( B ) Percentages of CC10-positive Clara cells that express p16, CC10-positive Clara cells that express phospho-p38 MAPK, and CC10-positive Clara cells that express both p16 and phospho-p38 MAPK in the lungs of COPD patients ( C : n = 14), asymptomatic smokers ( S : n = 7), and asymptomatic nonsmokers ( NS : n = 8). ( C ) Correlation between the percentage of CC10-positive Clara cells that express p16 and the percentage of CC10-positive Clara cells that express phospho-p38 MAPK. Open circles = asymptomatic nonsmokers; open triangles = asymptomatic smokers; closed circles = COPD patients. ( D ) Rates of immunopositivity for phospho-p38 MAPK in CC10-positive Clara cells that express p16 (senescent Clara cells) and in CC10-positive Clara cells that do not express p16 (presenescent Clara cells) in the subjects as a whole, asymptomatic nonsmokers, asymptomatic smokers, and COPD patients.

Article Snippet: The p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190 (Enzo Life Sciences, Plymouth Meeting, PA) or 0.1% DMSO was administered by intraperitoneal injection 30 minutes before each BrdU injection.

Techniques: Activation Assay, Immunofluorescence, Staining

Journal: Respiratory Research

Article Title: Epithelial cell senescence impairs repair process and exacerbates inflammation after airway injury

doi: 10.1186/1465-9921-12-78

Figure Lengend Snippet: Senescence of NCI-H441 cells after exposure to BrdU for 10 days is accompanied by p38 MAPK-dependent pro-inflammatory cytokine production . ( A ) ELISA to measure concentrations of IL-6, TNF-α, and GM-CSF in the culture supernatants of NCI-H441 cells exposed or not exposed to 25 μM of BrdU in the presence or absence of 10 μM of the p38 MAPK inhibitor SB202190. The concentration of the anti-inflammatory cytokine IL-10 was below the limit of detection. ( B ) Immunoblot analyses for phosphorylation levels of p38 MAPK and NF-κB in the cell lysates. ( C ) Effects of SB202190 on BrdU-induced SA β-gal activation and growth arrest. Data are expressed as the means ± SEM. N = 3-6 in each experiment.

Article Snippet: The p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190 (Enzo Life Sciences, Plymouth Meeting, PA) or 0.1% DMSO was administered by intraperitoneal injection 30 minutes before each BrdU injection.

Techniques: Enzyme-linked Immunosorbent Assay, Concentration Assay, Activation Assay

Journal: Respiratory Research

Article Title: Epithelial cell senescence impairs repair process and exacerbates inflammation after airway injury

doi: 10.1186/1465-9921-12-78

Figure Lengend Snippet: Pathways by which BrdU impairs epithelial repair and induces persistent inflammation in the chronic NA injury model . BrdU induces genotoxic stress, which activates the DNA damage response, thereby promoting premature senescence, which results in the growth arrest of epithelial cells. Genotoxic stress caused by BrdU also activates p38-MAPK pathways that trigger the production of pro-inflammatory cytokines/chemokines, which exacerbate inflammation. Which is necessary for p38-MAPK activation, the DNA damage response or cell cycle arrest (p21, etc.), has not been determined ( broken arrows ). Recent evidence indicates that pro-inflammatory cytokines (e.g., IL-6, IL-8) at least in part reinforce cell cycle arrest via the DNA damage response pathway [ 32 , 33 ], suggesting a positive feedback loop ( dashed arrow ) in which inflammation in turn promotes senescence.

Article Snippet: The p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190 (Enzo Life Sciences, Plymouth Meeting, PA) or 0.1% DMSO was administered by intraperitoneal injection 30 minutes before each BrdU injection.

Techniques: Activation Assay