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Inflammatory cytokines modulate chemokine production patterns of HepG2 cells toward initially inclined direction
Author(s) -
Ohashi Tomohiko,
Tanabe Junichi,
Ishikawa Tetsuya,
Okumura Akihiko,
Sato Ken,
Ayada Minoru,
Hotta Naoki,
Kuzuya Teiji,
Ito Hiroyasu,
Nakao Haruhisa,
Yoneda Masashi,
Kakumu Shinichi
Publication year - 2009
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2008.00482.x
Subject(s) - cxcl10 , cxcl9 , chemokine , ccl5 , ccl17 , cxcl16 , cytokine , interleukin 8 , ccl2 , cxcl14 , cxcl2 , immune system , ccl7 , immunology , microbiology and biotechnology , biology , t cell , chemokine receptor , il 2 receptor
Aim: Human hepatocytes are known to express an array of inflammatory cytokines and chemokines. In this study, we examined the potential roles of hepatocytes in regulating immune responses in the liver, by assessing the induction of Th1‐ or Th2‐specific chemokines in HepG2 cells after various inflammatory stimulations. Methods: HepG2 cells were stimulated with IL‐1α, IFN‐γ, IL‐4, IL‐10, and/or CCL2, harvested at several time points, and served for the analyses of cytokine/chemokine mRNA expressions by semi‐quantitative RT‐PCR. Results: (i) IL‐1α up‐regulated mRNA levels of CXCL8, CXCL10, and CCL2. IFN‐γ increased those of CXCL9, CXCL10, and CCL5, while IL‐4 or IL‐10 had no effect. (ii) Addition of IL‐4 to the culture of IFN‐γ‐stimulated cells, down‐regulated CXCL9 and CXCL10 mRNA levels. (iii) Addition of IFN‐γ to the culture of IL‐1α‐stimulated cells, further up‐regulated CXCL9 and CXCL10 mRNA levels. Addition of IL‐4 decreased CXCL8 and CXCL10 levels, and increased CCL2 level in IL‐1α‐stimulated cells. (iv) CCL2 induced IL‐4 mRNA expression. Conclusions: IFN‐γ augmented mRNA expression of Th1‐specific chemokines (CXCL9 and CXCL10) in HepG2 cells. IL‐4 had no effect on those of Th2‐spesific chemokines (CCL17 and CCL22); however, it was supposed to augment Th2 response indirectly through the induction of CCL2 under the inflammatory condition. The findings suggest that hepatocytes have ability to promote immune responses in the liver toward the direction, initially determined by the cytokine balances in the local inflammatory region.