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S100A11, an dual mediator for growth regulation of human keratinocytes.

ABSTRACT: We previously revealed a novel signal pathway involving S100A11 for inhibition of the growth of normal human keratinocytes (NHK) caused by high Ca(++) or transforming growth factor beta. Exposure to either agent resulted in transfer of S100A11 to nuclei, where it induced p21(WAF1). In contrast, S100A11 has been shown to be overexpressed in many human cancers. To address this apparent discrepancy, we analyzed possible new functions of S100A11, and we provide herein evidence that 1) S100A11 is actively secreted by NHK; 2) extracellular S100A11 acts on NHK to enhance the production of epidermal growth factor family proteins, resulting in growth stimulation; 3) receptor for advanced glycation end products, nuclear factor-kappaB, Akt, and cAMP response element-binding protein are involved in the S100A11-triggered signal transduction; and 4) production and secretion of S100A11 are markedly enhanced in human squamous cancer cells. These findings indicate that S100A11 plays a dual role in growth regulation of epithelial cells.

SUBMITTER: Sakaguchi M

PROVIDER: S-EPMC2174196 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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S100A11, an dual mediator for growth regulation of human keratinocytes.

Sakaguchi Masakiyo M Sonegawa Hiroyuki H Murata Hitoshi H Kitazoe Midori M Futami Jun-ichiro J Kataoka Ken K Yamada Hidenori H Huh Nam-ho NH

Molecular biology of the cell 20071031 1

We previously revealed a novel signal pathway involving S100A11 for inhibition of the growth of normal human keratinocytes (NHK) caused by high Ca(++) or transforming growth factor beta. Exposure to either agent resulted in transfer of S100A11 to nuclei, where it induced p21(WAF1). In contrast, S100A11 has been shown to be overexpressed in many human cancers. To address this apparent discrepancy, we analyzed possible new functions of S100A11, and we provide herein evidence that 1) S100A11 is act ...[more]

PMID: 17978094

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Project description:BackgroundCalgizzarin (S100A11) is a member of the S100 protein family that acts in different tumors by regulating a number of biologic functions. Recent data suggest its association with low-grade inflammation in osteoarthritis (OA). The aim of our study is to compare S100A11 expression in the synovial tissues, synovial fluid and serum of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to characterize the potential association between S100A11 and disease activity.MethodsS100A11 protein expression was detected in synovial tissue from patients with RA (n?=?6) and patients with OA (n?=?6) by immunohistochemistry and immunofluorescence. Serum and synovial fluid S100A11 levels were measured by ELISA in patients with RA (n?=?40) and patients with OA (n?=?34). Disease activity scores in 28 joints based on C-reactive protein (DAS28-CRP) were used to assess disease activity. Cytokine content in peripheral blood mononuclear cells (PBMCs), synovial fibroblasts (SFs) and synovial fluid was analysed by ELISA, western blotting or cytometric bead array.ResultsS100A11 expression was significantly up-regulated in the synovial lining and sublining layers (p?<?0.01) and vessels (p?<?0.05) of patients with RA compared to patients with OA, and was associated with fibroblasts and T cells. S100A11 was significantly increased in synovial fluid (p?<?0.0001) but not in serum (p?=?0.158) from patients with RA compared to patients with OA when adjusted for age and sex. Synovial fluid S100A11 correlated with DAS28 (r?=?0.350, p?=?0.027), serum CRP (r?=?0.463, p?=?0.003), synovial fluid leukocyte count (r?=?0.677, p?<?0.001), anti-cyclic citrullinated peptide antibodies (anti-CCP) (r?=?0.424, p?=?0.006) and IL-6 (r?=?0.578, p?=?0.002) and IL-8 (r?=?0.740, p?<?0.001) in synovial fluid from patients with RA. PBMCs and SFs isolated from patients with RA synthesized and spontaneously secreted higher levels of S100A11 in comparison with PBMCs and SFs from patients with OA (p?=?0.011 and 0.03, respectively). S100A11 stimulated the production of the pro-inflammatory cytokine IL-6 by PBMCs (p?<?0.05) and SFs (p?<?0.01).ConclusionsOur data provide the first evidence of S100A11 up-regulation and its association with inflammation and disease activity in patients with RA.

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S100A11, an dual mediator for growth regulation of human keratinocytes.

Publications

S100A11, an dual mediator for growth regulation of human keratinocytes.

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