Inflammasome Signaling Pathway NLRP3, IL1B, CASP1 what else?

NLRP3 inflammasome is a multimeric cytosolic protein complex that assembles in response to cellular perturbations.

Activation of this complex is regulated through two-step process, with priming at the transcriptional and posttranslational levels (Signal 1) and assembly by multiple pathways in response to a variety of exogenous pathogen-derived or endogenous danger molecules (Signal 2). This assembly leads to the activation of caspase-1, which promotes maturation and release of the inflammatory cytokines interleukin-1β (IL-1β) and IL-18, as well as inflammatory cell death (pyroptosis) ⁽¹⁾.

NLRP3-inflammasome-Mechanism-of-activation.

Mechanism of NLRP3 inflammasome activation ⁽¹⁾ .

We also cite the important role of NLRP3 complex in the antiviral immune responses. This complex can be activated by both viral components, including RNA and proteins (PAMPs), and danger signals (DAMPs)⁽⁵⁾.

NLRP3 complex and diseases

The NLRP3 complex play dual roles in mediating a wide range of human disease like: inflammatory, metabolic (atherosclerosis, nonalcoholic fatty liver disease (NAFLD), gout, type 2 diabetes and obesity induced insulin resistance.), chronic neurodegenerative diseases, and COVID-19... Without ignoring their beneficial role in numerous infectious diseases and some cancers ^(1,3,4).

(1) Sharma BR, Kanneganti TD. NLRP3 inflammasome in cancer and metabolic diseases. Nat Immunol. (2021);22(5):550-559.

(2) Paik S et al. An update on the regulatory mechanisms of NLRP3 inflammasome activation. Cell Mol Immunol. (2021);18(5):1141-1160.

(3) Wang L, Hauenstein AV. The NLRP3 inflammasome: Mechanism of action, role in disease and therapies. Mol Aspects Med. (2020);76:100889.

(4) Zhao N, Di B, Xu LL. The NLRP3 inflammasome and COVID-19: Activation, pathogenesis and therapeutic strategies. Cytokine Growth Factor Rev. (2021);61:2-15.

(5) Zhao C, Zhao W. NLRP3 Inflammasome-A Key Player in Antiviral Responses. Front Immunol. (2020)18;11:211.

Species : Homo sapiens (human)

Human Inflammasome Signaling Pathway

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Species : Mus musculus (mouse)

Mouse Inflammasome Signaling Pathway

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Species : Rattus norvegicus (rat)

Rat Inflammasome Signaling Pathway

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Species : Sus Scrofa (Pig)

Pig Inflammasome Signaling Pathway

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