Interleukin-1β (IL-1β) Processing Pathway

Abstract

The innate immune system senses molecular patterns from invading microorganisms. Once activated, it orchestrates the inflammatory response by secreting proinflammatory cytokines, such as interleukin-1 (IL-1)-type cytokines, in particular IL-1beta. IL-1 mediates the expression of a vast array of genes involved in secondary inflammation. IL-1-responsive genes coordinate all aspects of local inflammation and also attract and activate cells of the adaptive immune system at sites of infection. Moreover, the innate immune system can also sense a wide range of nonmicrobial molecular patterns that represent danger or damage signals. These signals activate the NALP3-inflammasome pathway, which plays a central role in acute and chronic sterile inflammation. Here, we describe the essential components of the NALP3-inflammasome that control processing and release of IL-1beta.

Interleukin-1β (IL-1β) promotes susceptibility of Toll-like receptor 5 (TLR5) deficient mice to colitis

“…In light of its potency, IL-1β activity is regulated at multiple levels including transcription of the pro-IL-1β gene, the inflammasome-mediated maturation of pro-IL1β into mature IL-1β and modulation of IL-1β activity via regulated expression of sIL-1Ra 39 40. Loss of TLR5 might contribute to elevated IL-1β activity at all of these levels 14.…”

Regulation of Cytokine and Chemokine Expression by the Ribotoxic Stress Response Elicited by Shiga Toxin Type 1 in Human Macrophage-Like THP-1 Cells

“…As we have previously noted (18), there was no direct correlation between Stx1-induced IL-1␤ transcript and protein expression; we detected a Ͼ300-fold increase in IL-1␤ mRNA, while protein levels were increased only ϳ10-fold. The precise mechanisms responsible for the differential expression of IL-1␤ transcript and protein remain to be characterized, although it is known that IL-1␤ protein undergoes extensive posttranslational processing prior to secretion (65).…”

Neutrophil Elastase, Proteinase 3, and Cathepsin G as Therapeutic Targets in Human Diseases

“…Processing of Cytokines, Chemokines, and Growth Factors. TNF-␣ and IL-1␤ are inflammatory cytokines synthesized as inactive membrane-bound pro-forms and are converted to their active forms by the metalloprotease TNF-␣ converting enzyme (Black et al, 1997) and by the cysteine protease IL-1␤-converting enzyme (caspase-1) (Black et al, 1988;Weber et al, 2010), respectively. PR3, however, can also cleave the proforms of TNF-␣ and IL-1␤ at Val-Arg bonds (Robache-Gallea et al, 1995;Coeshott et al, 1999).…”