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Suppressing IL-32 in monocytes impairs the induction of the proinflammatory cytokines TNFalpha and IL-1beta

Targeting major proinflammatory cytokines such as IL-1beta and TNFalpha is of great interest in patients with chronic inflammatory diseases, including rheumatoid arthritis, colitis, and psoriasis. The cytokine Interleukin (IL)-32 induces proinflammatory cytokines such as TNFalpha, IL-1beta, IL-6, an...

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Published in:Cytokine (Philadelphia, Pa.) Pa.), 2010-02, Vol.49 (2), p.171-176
Main Authors: Hong, Jaewoo, Bae, Suyoung, Kang, Youngsun, Yoon, Doyoung, Bai, Xiyuan, Chan, Edward D, Azam, Tania, Dinarello, Charles A, Lee, Siyoung, Her, Erk, Rho, Gyujin, Kim, Soohyun
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Language:English
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Summary:Targeting major proinflammatory cytokines such as IL-1beta and TNFalpha is of great interest in patients with chronic inflammatory diseases, including rheumatoid arthritis, colitis, and psoriasis. The cytokine Interleukin (IL)-32 induces proinflammatory cytokines such as TNFalpha, IL-1beta, IL-6, and chemokines. We previously used an IL-32 ligand-affinity column to purify proteinase 3, which is abundantly expressed in neutrophil and monocytic leukocytes but not in other cell types, and found that IL-32 is mainly produced by monocytic leukocytes. This evidence suggested that silencing endogenous IL-32 by short hairpin RNA (shRNA) in monocytic cells might reveal the precise function of endogenous IL-32. Indeed, lipopolysaccharide (LPS)- or phorbol myristate acetate (PMA)-induced proinflammatory cytokine production was significantly inhibited in shRNA/IL-32 stable clones as compared to control clones. Furthermore, macrophages in PMA-differentiated shRNA/IL-32 stable clones displayed remarkably impaired LPS- and IL-1beta-induced proinflammatory cytokine production. These data suggest that IL-32 is not only involved in host defense against pathogens, but also might play a role in chronic inflammatory diseases. IL-32 production leads to major proinflammatory cytokine production during the initial immune response.
ISSN:1096-0023
DOI:10.1016/j.cyto.2009.10.003