IADR Abstract Archives

IL-1a and KGF regulate keratinocyte expression of antimicrobial peptides

Objectives: Epithelial cells express antimicrobial peptides (AMPs) and contribute to host defense through the innate immune system. We reported that IL-1α up-regulated the expression of some AMPs including lipocalin 2 (LCN2), S100A7, calprotectin (S100A8/S100A9), β-defensin (hBD-2) and secretory leukocyte protease inhibitor (SLPI). Interleukin 1-α (IL-1α) is also produced by keratinocytes and regulates keratinocyte differentiation. The growth and differentiation of keratinocytes is stimulated by keratinocyte growth factor (KGF), which is expressed by fibroblasts. In the present study, we investigated the effect of IL-1α and KGF on the expression of AMPs in human keratinocytes, and the regulatory mechanism of calprotectin expression by IL-1α and fibroblast-derived KGF.

Methods: The immortalized human keratinocyte cell line (HaCaT) were cultured to 90%-confluence and then incubated with IL-1α or KGF for 48 h in the presence or absence of MAPK (p38, ERK, JNK) inhibitors. Normal human skin fibroblasts (NB1RGB) were cultured with IL-1α for 24 h. Expression of AMP-specific mRNAs, including S100A7, S100A8, S100A9, LCN2, SLPI and hBD-2, was estimated by Northern blotting and RT-PCR. Calprotectin protein concentration was estimated by ELISA and MAPK phosphorylation was analyzed by Western blotting.

Results: IL-1α increased KGF mRNA expression in fibroblasts and KGF up-regulated IL-1α mRNA expression in keratinocytes. In a pattern that differed from IL-1α, KGF decreased expression of S100A7, S100A8 and S100A9 mRNAs, increased LCN2 and SLPI, but did not affect hBD-2. IL-1α increased and KGF decreased expression of calprotectin protein. IL-1α-induced S100A8/S100A9 expression was p38 phosphorylation-dependent. KGF-induced down-regulation of S100A8/S100A9 was ERK phosphorylation-dependent.

Conclusion: These results suggest that IL-1α and KGF modulate AMP expression in keratinocytes through different signaling pathways.

Supported by NIH R01DE11831 (MCH) and Grants-in-Aid (#19592388) for Scientific Research from the Japan Society for the Promotion of Science.

Division: IADR/CADR General Session
Meeting: 2008 IADR/CADR General Session (Toronto, Ontario, Canada)
Location: Toronto, Ontario, Canada
Year: 2008
Final Presentation ID: 3480
Abstract Category|Abstract Category(s): Periodontal Research - Pathogenesis

Authors

Bando, Mika ( Periodontology and Endodontology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, N/A, Japan )

Hiroshima, Yuka ( Periodontology and Endodontology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, N/A, Japan )

Kataoka, Masatoshi ( Health Technology Research Center, Nano-bioanalysis Team, National Institute of Advanced Industrial Science and Technology, Takamatsu, N/A, Japan )

Herzberg, Mark C. ( University of Minnesota, Minneapolis, MN, USA )

Ross, Karen F. ( University of Minnesota, Minneapolis, MN, USA )

Nagata, Toshihiko ( Periodontology and Endodontology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, N/A, Japan )

Kido, Jun-ichi ( Periodontology and Endodontology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, N/A, Japan )

SESSION INFORMATION

Poster Session
Inflammatory Response
07/05/2008