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, 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.
Hong
Jaewoo
J
Laboratory of Cytokine Immunology, Medical Immunology Center, Institute of Biomedical Science and Technology, Konkuk University 1 Hwayang dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
Bae
Suyoung
S
Kang
Youngsun
Y
Yoon
Doyoung
D
Bai
Xiyuan
X
Chan
Edward D
ED
Azam
Tania
T
Dinarello
Charles A
CA
Lee
Siyoung
S
Her
Erk
E
Rho
Gyujin
G
Kim
Soohyun
S
D000818:Animals; D002460:Cell Line; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
C496971:IL32 protein, human; D053583:Interleukin-1beta; D007378:Interleukins; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha