title: Regulation of matrix metalloproteinase-1 and alpha-smooth muscle actin expression by interleukin-1 alpha and tumour necrosis factor alpha in hepatic stellate cells.
abstract: Hepatic stellate cells (HSCs) are key players in liver fibrosis and regeneration via collagen degradation and synthesis. These phenomena involve inflammatory cytokines released from non-parenchymal liver cells such as Kupffer cells. Although the effects of individual cytokines on many cell types have been investigated in various conditions, such as inflammation and tissue fibrosis, investigating the effect of combined cytokines would further our understanding of the regulatory mechanisms in tissue fibrosis. Here, we report the effect of multiple cytokine combinations on primary HSCs. We first examined the effect of individual cytokines and then the simultaneous exposure of different cytokines, including interleukin-6 (IL-6), IL-1 alpha (IL-1α), platelet-derived growth factor (PDGF), tumour necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β), on matrix metalloproteinase-1 (MMP1) gene expression in primary HSCs. We observed that the combination of all five cytokines induced higher levels of MMP1 gene expression. Of these cytokines, TNF-α and IL-1α were found to be the key cytokines for not only inducing MMP1 expression, but also increasing α-smooth muscle actin gene expression. In conclusion, the combined treatment of TNF-α and IL-1α on HSCs had an enhanced effect on the expression of the fibrotic genes, MMP1 and α-smooth muscle actin, so appears to be an important regulator for tissue regeneration. This finding suggests that stimulation with combined anti-fibrotic cytokines is a potential approach in the development of a novel therapy for the recovery of liver fibrosis.
authors.affiliation: Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka-shi, Fukuoka, 819-0395, Japan.
authors.forename: Asami
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka-shi, Fukuoka, 812-8581, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Obayashi
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka-shi, Fukuoka, 812-8581, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sonoda
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: Asakura Medical Association Hospital, 422-1 Raiha, Asakura, Fukuoka, 838-0069, Japan.
authors.forename: Takato
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka-shi, Fukuoka, 819-0395, Japan.|Department of Bioscience and Biotechnology, Faculty of agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka-shi, Fukuoka, 812-8581, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kuhara
authors.affiliation: Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka-shi, Fukuoka, 819-0395, Japan. ktashiro@grt.kyushu-u.ac.jp.|Department of Bioscience and Biotechnology, Faculty of agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka-shi, Fukuoka, 812-8581, Japan. ktashiro@grt.kyushu-u.ac.jp.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tashiro
keywords: Hepatic stellate cell; IL-1α; Liver fibrosis; TNF-α
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