Journal: Inflammation

Article Title: Targeting Cold-Inducible RNA-Binding Protein Attenuates Pancreatic Fibrosis by Suppressing Pyroptosis in Chronic Pancreatitis

doi: 10.1007/s10753-026-02490-x

Figure Lengend Snippet: Inflammation and pyroptosis were increased in CP mice. Cerulein-CP was induced by 6 IP injections of cerulein (50 µg/kg/body weight) twice a week for 10 weeks. L-arginine-CP was induced by 2 hourly IP injections of 4.0 g/kg L-arginine twice a week for 10 weeks. The animals were sacrificed at 10 weeks after the first injection of L-arginine or cerulein. Blood and tissue samples were collected. ( A-C ) Representative photos and quantitative of F4/80 and CD11b staining; ( D ) Serum IL-6 level; ( E ) Serum TNF-α level; ( F & G ) Western blot analysis and quantitative of the expression of NLRP3 in the pancreas; ( H ) Serum IL-18 level; ( I ) Serum IL-1β level; ( J ) Correlation analysis of serum IL-18 and Masson positive aera; ( K ) Correlation analysis of serum IL-1β and Masson positive aera; ( L ) Correlation analysis of serum CIRP and F4/80 positive cells; ( M ) Correlation analysis of serum CIRP and CD11b positive cells; ( N ) Correlation analysis of serum CIRP and F4/80 positive cells; ( O ) Correlation analysis of serum CIRP and CD11b positive cells; ( R ) Correlation analysis of serum CIRP and IL-18; ( S ) Correlation analysis of serum CIRP and IL-1β; ( T ) Correlation analysis of serum CIRP and serum IL-18 in CP patients; ( U ) Correlation analysis of serum CIRP and serum IL-1β in CP patients; ( V ) Correlation analysis of serum CIRP and serum HMGB1 in CP patients. Data are presented as mean ± SD ( n = 6 per group). Statistical analyses were performed using GraphPad Prism 8.0. Statistical significance was determined by t-test or one-way ANOVA with Tukey’s post-hoc test. Correlations were assessed using Spearman’s rank correlation coefficient. * P < 0.05 indicates a statistically significant difference. CP, chronic pancreatitis; CIRP, Cold-inducible RNA-binding protein; L-arg, L-arginine; Cer, Cerulein; IL-6, interleukin 6; TNF-α, tumor necrosis factor-α; NLRP3, Nod-like receptor family protein 3; IL-18, interleukin 18; IL-1β, HMGB1, high mobility group protein B1; interleukin 1β

Article Snippet: In the other groups of experimental CP, normal saline (vehicle) or 5, 20 or 100 mg/kg NLRP3 inhibitor [ ] (S3680, Selleck, Inc. CN) was administered by intraperitoneal injection 2 h after the last injection of L-arginine or cerulein.

Techniques: Injection, Staining, Western Blot, Expressing, RNA Binding Assay

Journal: Inflammation

Article Title: Targeting Cold-Inducible RNA-Binding Protein Attenuates Pancreatic Fibrosis by Suppressing Pyroptosis in Chronic Pancreatitis

doi: 10.1007/s10753-026-02490-x

Figure Lengend Snippet: CIRP deficiency alleviates inflammation and pyroptosis in CP model mice. Cerulein-CP was induced by 6 IP injections of cerulein (50 µg/kg/body weight) twice a week for 10 weeks. L-arginine-CP was induced by 2 hourly IP injections of 4.0 g/kg L-arginine twice a week for 10 weeks. 8 mg/kg C23 was administered 2 h after the last L-arginine or cerulein injection each time. To determine the role of TLR4 in CIRP’s effect in CP, TAK-242, a specific TLR4 receptor inhibitor, were administered through intraperitoneal injection at 1 h after the last injection of L-arginine or cerulein each time. The animals were sacrificed 10 weeks after the first injection of L-arginine or cerulein. Blood and tissue samples were collected. ( A & B ) Western blot analysis and quantitative of the expression of NLRP3, Cleaved Caspase-1 and Cleaved Gasdermin D in the pancreas; ( C-E ) Representative photos and quantitative of F4/80 and CD11b staining; ( F ) Serum IL-1β level; ( G ) Serum IL-18 level; ( H-J ) Western blot analysis and quantitative of the expression of NLRP3 and Cleaved Gasdermin D in the pancreas; ( K & L ) Representative photos and quantitative of F4/80 staining. Data are presented as mean ± SD ( n = 6 per group). Statistical analyses were performed using GraphPad Prism 8.0. Data were analyzed by one-way ANOVA with Tukey’s post-hoc test. * P < 0.05 indicates a statistically significant difference. CP, chronic pancreatitis; CIRP, Cold-inducible RNA-binding protein; KO, knockout; L-arg, L-arginine; NLRP3, Nod-like receptor family protein 3; TLR4, Toll-like receptor 4; IL-18, interleukin 18; IL-1β, interleukin 1β; Cer, Cerulein

Article Snippet: In the other groups of experimental CP, normal saline (vehicle) or 5, 20 or 100 mg/kg NLRP3 inhibitor [ ] (S3680, Selleck, Inc. CN) was administered by intraperitoneal injection 2 h after the last injection of L-arginine or cerulein.

Techniques: Injection, Western Blot, Expressing, Staining, RNA Binding Assay, Knock-Out

Journal: Inflammation

Article Title: Targeting Cold-Inducible RNA-Binding Protein Attenuates Pancreatic Fibrosis by Suppressing Pyroptosis in Chronic Pancreatitis

doi: 10.1007/s10753-026-02490-x

Figure Lengend Snippet: NLRP3 inhibitor alleviates inflammation and pancreatic fibrosis in Experimental CP. Cerulein-CP was induced by 6 IP injections of cerulein (50 µg/kg/body weight) twice a week for 10 weeks. L-arginine-CP was induced by 2 hourly IP injections of 4.0 g/kg L-arginine twice a week for 10 weeks. At 2 h after the last injection of L-arginine or cerulein each time, normal saline (vehicle) or 5, 20, 100 mg/kg NLRP3 inhibitor was administered by intraperitoneal injection. The animals were sacrificed 10 weeks after the first injection of L-arginine or cerulein. Blood and tissue samples were collected. ( A ) Western blot analysis of the expression of CIRP, NLRP3, Cleaved Caspase-1 and Cleaved Gasdermin D in the pancreas; ( B ) Serum IL-1β level; ( C ) Serum IL-6 level; ( D-G ) Representative photos and quantitative of H&E, Sirius red and F4/80 staining; ( H ) Serum HMGB1 level. Data are presented as mean ± SD ( n = 6 per group). Statistical analyses were performed using GraphPad Prism 8.0. Data were analyzed by one-way ANOVA with Tukey’s post-hoc test. * P < 0.05 indicates a statistically significant difference. CP, chronic pancreatitis; CIRP, Cold-inducible RNA-binding protein; NLRP3, Nod-like receptor family protein 3; IL-6, interleukin 6; IL-1β, interleukin 1β; HMGB1, high mobility group protein B1; Cer, Cerulein; L-arg, L-arginine

Article Snippet: In the other groups of experimental CP, normal saline (vehicle) or 5, 20 or 100 mg/kg NLRP3 inhibitor [ ] (S3680, Selleck, Inc. CN) was administered by intraperitoneal injection 2 h after the last injection of L-arginine or cerulein.

Techniques: Injection, Saline, Western Blot, Expressing, Staining, RNA Binding Assay

Journal: Inflammation

Article Title: Targeting Cold-Inducible RNA-Binding Protein Attenuates Pancreatic Fibrosis by Suppressing Pyroptosis in Chronic Pancreatitis

doi: 10.1007/s10753-026-02490-x

Figure Lengend Snippet: Gasdermin D inhibitor alleviates inflammation and pancreatic fibrosis in Experimental CP. Cerulein-CP was induced by 6 IP injections of cerulein (50 µg/kg/body weight) twice a week for 10 weeks. L-arginine-CP was induced by 2 hourly IP injections of 4.0 g/kg L-arginine twice a week for 10 weeks. At 2 h after the last injection of L-arginine or cerulein each time, normal saline (vehicle) or 5, 20, 50 mg/kg Disulfiram, a potent gasdermin D inhibitor, was administered by intraperitoneal injection. The animals were sacrificed 10 weeks after the first injection of L-arginine or cerulein. Blood and tissue samples were collected. ( A-D ) Representative photos and quantitative of H&E, Sirius red and F4/80 staining; ( E ) Western blot analysis of the expression of CIRP, NLRP3 and Cleaved Gasdermin D in the pancreas; ( F ) Serum IL-18 level. Data are presented as mean ± SD ( n = 6 per group). Statistical analyses were performed using GraphPad Prism 8.0. Data were analyzed by one-way ANOVA with Tukey’s post-hoc test. * P < 0.05 indicates a statistically significant difference. CP, chronic pancreatitis; CIRP, Cold-inducible RNA-binding protein; NLRP3, Nod-like receptor family protein 3; IL-18, interleukin 18

Article Snippet: In the other groups of experimental CP, normal saline (vehicle) or 5, 20 or 100 mg/kg NLRP3 inhibitor [ ] (S3680, Selleck, Inc. CN) was administered by intraperitoneal injection 2 h after the last injection of L-arginine or cerulein.

Techniques: Injection, Saline, Staining, Western Blot, Expressing, RNA Binding Assay

Journal: Diabetologia

Article Title: Targeting the NLRP3 inflammasome–IL-1β pathway in type 2 diabetes and obesity

doi: 10.1007/s00125-024-06306-1

Figure Lengend Snippet: Schematic overview of canonical IL-1β production and secretion. TLR2, TLR4 and IL-1 signalling prime myeloid cells, starting the transcription of inflammasome components (e.g. PYCARD [ASC], NLRP3 ) and IL-1-responsive genes (e.g. IL1B , IL1RN [IL-1RA], CXCL8 [IL-8], IL6 ). Glucose, K + efflux, and DAMPs and PAMPs trigger intracellular stimuli that act as a second signal activating the NLRP3 inflammasome. Elevated cytosolic levels of reactive oxygen species (ROS), islet amyloid polypeptide (IAPP) and ATP activate NLRP3 receptors. ROS and crystalline substances such as cholesterol and uric acid disrupt the lysosomal membrane in phagocytes, promoting leakage of lysosome cargo into the cytosol, releasing epitopes that are recognised by the LRR domain of the NLRP3 receptor. The NLRP3 inflammasome is composed of the sensor NLRP3, the adaptor protein ASC and the effector molecule caspase-1. On receiving a second stimulus, the NLRP3 inflammasome is assembled in the cytosol, leading to the activation of caspase-1 and subsequent secretion of active IL-1β via the gasdermin D pore. After being secreted, IL-1β binds to the IL-1R1, amplifying intracellular inflammatory signalling and transcription of NLRP3 inflammasome components. TCA, tricarboxylic acid. This figure is available as part of a downloadable slideset

Article Snippet: Olatec provides the authors with an NLRP3 inhibitor used for an ongoing clinical study funded by a European Union/Swiss grant.

Techniques: Membrane, Activation Assay

Journal: Diabetologia

Article Title: Targeting the NLRP3 inflammasome–IL-1β pathway in type 2 diabetes and obesity

doi: 10.1007/s00125-024-06306-1

Figure Lengend Snippet: Role of the NLRP3 inflammasome–IL-1β pathway in the pathogenesis of metabolic diseases and comorbidities. Metabolic stress induced by NEFAs, glucose, cholesterol, uric acid and islet amyloid polypeptide (IAPP), along with ageing and changes in the microbiome, activate NLRP3 with subsequent cleavage of pro-IL-1β. In turn, IL-1β contributes to impaired insulin secretion, insulin resistance, MAFLD, atherosclerosis, heart failure, retinopathy, nephropathy, neuropathy, obesity, Alzheimer’s disease, fatigue, testosterone deficiency, polycystic ovary syndrome, rheumatoid arthritis and gout. Blocking IL-1 signalling or inhibition of NLRP3 counteracts pathologies associated with metabolic diseases. This figure is available as part of a downloadable slideset

Article Snippet: Olatec provides the authors with an NLRP3 inhibitor used for an ongoing clinical study funded by a European Union/Swiss grant.

Techniques: Blocking Assay, Inhibition

Journal: Diabetologia

Article Title: Targeting the NLRP3 inflammasome–IL-1β pathway in type 2 diabetes and obesity

doi: 10.1007/s00125-024-06306-1

Figure Lengend Snippet: Clinical studies of NLRP3 inhibition or IL-1 antagonism for the treatment of type 2 diabetes and its complications

Article Snippet: Olatec provides the authors with an NLRP3 inhibitor used for an ongoing clinical study funded by a European Union/Swiss grant.

Techniques: Inhibition, Drug discovery