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IL-1 β genesis: the art of regulating the regulator

Cellular & Molecular Immunology volume 15, pages 998–1000 (2018)Cite this article

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In a study published in Cellular and Molecular Immunology, Singh et al. demonstrated a new mechanism of monocyte IL-1β production.1 It was observed that TLR-4- and TLR-2-induced IRAK-ERK pathway cross-talk with p67phox-Nox-2 for reactive oxygen species (ROS) generation, thus regulating IL-1β transcription and processing in monocytes. This study not only establishes a direct link between IRAK and ERK, but also demonstrates the regulation of p67phox-Nox-2 by ERK for ROS and IL-1β production (Fig. 1). This study shows that the IRAK-ERK axis can regulate both IL-β transcription and processing through ROS.

The monocyte activation by TLR ligands leads to the production of inflammatory cytokines such as IL-1β and TNF-α, which exert diverse roles.2 Due to its high potency and diverse effects, IL-1β can modulate the progression of various pathological disorders such as rheumatoid arthritis, aneurysm, type I diabetes, atherosclerosis, and airway inflammation. Therefore, understanding the mechanism of IL-1β production may help in designing therapeutic strategies for various inflammatory disorders. Secreted IL-1β binds to its receptor IL-1βR and induces a cascade of signaling events, including the activation of IRAK, MAPK, and NF-κB, leading to the transcription of various inflammatory cytokines and growth factors. IL-1β affects both the adaptive and innate immune responses. It affects T cell maturation and the proliferation of B cells. Further, IL-1β promotes the expression of several inflammatory molecules such as nitric oxide, phospholipase A2, cyclooxygenase-2, and prostaglandin E2.3

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Fig. 1

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  1. Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, UP, India

    Priya Gupta & Manoj K. Barthwal

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  1. Priya Gupta
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Gupta, P., Barthwal, M.K. IL-1 β genesis: the art of regulating the regulator. Cell Mol Immunol 15, 998–1000 (2018). https://doi.org/10.1038/s41423-018-0054-7

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