ID 109804
Title Transcription
ジョウヒ サイボウ ニオケル コウキン ペプチド ノ ハツゲン チョウセツ キコウ ノ カイメイ
Title Alternative
Regulation of Antimicrobial Peptide Expression in Human Keratinocytes
Author
Bando, Mika Department of Periodontology and Endodontology, Institute of Health Biosciences, The University of Tokushima Graduate School Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
上皮細胞
抗菌ペプチド
IL-1α
KGF
MAPK 経路
Content Type
Journal Article
Description
Epithelial cells express antimicrobial peptides (AMPs) including calprotectin (S100A8/S100A9), β-defensin and lipocalin, which contribute to a host defense reaction in the innate immune system. However, the regulation of AMP expression is not well elucidated. Interleukin1-α (IL-1α), an autonomous cytokine, regulates keratinocyte differentiation and also induces the expression of keratinocyte growth factor (KGF) in fibroblasts. It is reported that KGF stimulates the growth and differentiation of keratinocytes. I confirmed the expression of calprotectin in gingiva and skin by immunohistochemical staining, and determined the effect of IL-1α and KGF on the expression of several AMPs in human keratinocytes cell line (HaCaT) and human fibroblast cell line (NB1RGB), and then clarified the regulatory mechanism of calprotectin expression induced by IL-1α and KGF with the analyses of microarray, Northern blot, RT-PCR and Western blot. Immunohistochemical staining showed that calprotectin expressed in human normal gingiva and skin, and this expression increased in periodontitis gingivae and psoriasis skins. IL-1α increased KGF mRNA expression in NB1RGB, and KGF up-regulated IL-1α mRNA expression in HaCaT. Microarray analysis revealed that IL-1α increased some AMPs, lipocalin 2 (LCN2), S100A8, S100A9 and secretory leukocyte protease inhibitor (SLPI), showing more than 2-fold expressions in HaCaT. RT-PCR and Northern blot analysis revealed that IL-1α increased mRNA expressions of S100A7, S100A8, S100A9, LCN2, SLPI, and β-defensin 2 (hBD-2) in HaCaT. On the other hand, KGF decreased the expression of S100A7, S100A8, and S100A9, and increased LCN2 and SLPI expressions. KGF did not affect hBD-2 expression. When the inhibitors of mitogen-activated protein kinase (MAPK), including p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase (ERK) were added to HaCaT, p38 inhibitor suppressed the IL-1α-up-regulated S100A8/S100A9 expression and ERK inhibitor suppressed the KGF-down-regulated S100A8/S100A9 expression. These results indicate that some AMP expressions are regulated by IL-1α and KGF in human keratinocytes and that IL-1α up-regulates and KGF down-regulates S100A8/S100A9 genes through MAPK pathway in keratinocytes.
Journal Title
四国歯学会雑誌
ISSN
09146091
NCID
AN10050046
Publisher
四国歯学会
Volume
23
Issue
2
Start Page
97
End Page
102
Sort Key
97
Published Date
2011-01-31
FullText File
language
jpn
TextVersion
Publisher
departments
University Hospital