Lipopolysaccharide-Mediated Induction of Concurrent IL-1β and IL-23 Expression in THP-1 Cells Exhibits Differential Requirements for Caspase-1 and Cathepsin B Activity.
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.
Department of Biomedical and Molecular Sciences, Queen's University , Kingston, Canada .
Christopher
C
Wynick
Department of Biomedical and Molecular Sciences, Queen's University , Kingston, Canada .
Carlene
C
Petes
Department of Biomedical and Molecular Sciences, Queen's University , Kingston, Canada .
Alexander
A
Tigert
Department of Biomedical and Molecular Sciences, Queen's University , Kingston, Canada .
Katrina
K
Gee
D000255:Adenosine Triphosphate / Q000378:metabolism; D015415:Biomarkers; D020170:Caspase 1 / Q000378:metabolism*; D002401:Cathepsin B / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
D015415:Biomarkers; D016207:Cytokines; D053583:Interleukin-1beta; D053759:Interleukin-23; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D000255:Adenosine Triphosphate; D002401:Cathepsin B; D020170:Caspase 1