J Interferon Cytokine Res
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada .
Published: August 2016
The inflammasome is a multimeric protein complex required for interleukin (IL)-1β production. Upon lipopolysaccharide (LPS) triggering of toll-like receptor (TLR)-4 and subsequent ATP signaling, the NOD-like receptor containing-pyrin domain 3 (NLRP3) inflammasome is activated to cleave pro-caspase-1 into caspase-1, allowing the secretion of IL-1β. IL-1β is known to function with IL-23 in the regulation of IL-17-producing CD4(+) T cells, Th17 cells, in adaptive immunity. Recently, studies have shown that IL-1β and IL-23 together activate IL-17-producing innate lymphoid cells, demonstrating that the pair may exhibit additional effects on cell differentiation. Using an in vitro model of bacterial infection, LPS treatment of human monocytic cells, we investigated the molecular mechanisms involved in the co-expression of IL-1β and IL-23. We found that IL-1β is partially required for optimal LPS-induced IL-23 production. We also found that IL-23 production was partially dependent on ATP signaling via the P2X7 receptor, whereas IL-1β production required this signaling. Furthermore, we identified a novel role for cathepsin B activity in IL-23 production. Taken together, this study identifies differential requirements for the co-expression of IL-1β and IL-23. Due to their similar roles in Th17 differentiation, characterization of the regulatory mechanisms for LPS-induced IL-1β and IL-23 may reveal novel information into the pathology of the inflammatory response particularly during bacterial infection.
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http://dx.doi.org/10.1089/jir.2015.0134 | DOI Listing |
PLoS One
January 2025
Center for Inflammation, Immunity, & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, United States of America.
Microbiota-induced production of IL-22 by type 3 innate lymphoid cells (ILC3) plays an important role in maintaining intestinal health. Such IL-22 production is driven, in part, by IL-23 produced by gut myeloid cells that have sensed select microbial-derived mediators. The extent to which ILC3 can directly respond to microbial metabolites via IL-22 production is less clear, in part due to the difficulty of isolating and maintaining sufficient numbers of viable ILC3 ex vivo.
View Article and Find Full Text PDFJ Crohns Colitis
January 2025
Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute; McMaster University, Hamilton ON, Canada.
Introduction: In inflammatory bowel disease (IBD), the number of eosinophils increases in the lamina propria of the intestinal tract, but their specific patho-mechanistic role remains unclear. Elevated blood eosinophil counts in active IBD suggest their potential as biomarkers for predicting response to biologic therapies. This study evaluates blood eosinophil count trends and their predictive value for clinical response and endoscopic improvement in patients with IBD receiving ustekinumab or adalimumab induction therapy.
View Article and Find Full Text PDFIL-17 and IL-23 inhibitors have shown successful results in improving skin lesions in the treatment of moderate-to-severe plaque psoriasis. However, psoriasis is a chronic inflammatory disease characterized by systemic inflammation including joints in addition to skin lesions. Therefore, in this retrospective and observational cohort study, we aimed to evaluate the effect of IL-17 inhibitors (secukinumab and ixekizumab) and IL-23 inhibitors (risankizumab and guselkumab) on systemic inflammation in psoriasis.
View Article and Find Full Text PDFArch Dermatol Res
January 2025
Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, USA.
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by pustules that rapidly progress into ulcers that commonly affect the lower limbs. Recently, successful treatment of PG has been reported with anti-IL 17 treatments. However, there have also been several reports of "paradoxical" induction of new PG lesions after use of IL-17 inhibitors.
View Article and Find Full Text PDFAnn Pharmacother
January 2025
Inflammatory Bowel Disease Center, The University of Chicago Medicine, Chicago, IL, USA.
Objective: To summarize the evidence and pharmacologic profile of guselkumab for moderate to severe ulcerative colitis (UC).
Data Sources: A PubMed search from inception to end of October 2024 using keywords was conducted. Additional information was obtained from abstracts and package insert.
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