title: Inflammatory cytokines modulate chemokine production patterns of HepG2 cells toward initially inclined direction.
abstract: OBJECTIVE
  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-1alpha, IFN-gamma, 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-1alpha up-regulated mRNA levels of CXCL8, CXCL10, and CCL2. IFN-gamma 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-gamma-stimulated cells, down-regulated CXCL9 and CXCL10 mRNA levels. (iii) Addition of IFN-gamma to the culture of IL-1alpha-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-1alpha-stimulated cells. (iv) CCL2 induced IL-4 mRNA expression.
  
  
  CONCLUSIONS
  IFN-gamma 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.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ohashi
authors.forename: Junichi
authors.initials: J
authors.lastname: Tanabe
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okumura
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.forename: Minoru
authors.initials: M
authors.lastname: Ayada
authors.forename: Naoki
authors.initials: N
authors.lastname: Hotta
authors.forename: Teiji
authors.initials: T
authors.lastname: Kuzuya
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ito
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Nakao
authors.forename: Masashi
authors.initials: M
authors.lastname: Yoneda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kakumu