Upregulation of MMP‐9 production by TNFα in keratinocytes and its attenuation by vitamin D

K. Bahar‐Shany; A. Ravid; R. Koren

doi:10.1002/jcp.22004

journal article Dec 17, 2009

Upregulation of MMP‐9 production by TNFα in keratinocytes and its attenuation by vitamin D

K. Bahar‐Shany A. Ravid R. Koren

Journal of Cellular Physiology Vol. 222 No. 3 pp. 729-737 · Wiley

View at Publisher Save 10.1002/jcp.22004

Abstract

AbstractMMP‐9, a member of the matrix metalloproteinase family that degrades collagen IV and processes chemokines and cytokines, participates in epidermal remodeling in response to stress and injury. Limited activity of MMP‐9 is essential while excessive activity is deleterious to the healing process. Tumor necrosis factor (TNFα), a key mediator of cutaneous inflammation, is a powerful inducer of MMP‐9. Calcitriol, the hormonally active vitamin D metabolite, and its analogs are known to attenuate epidermal inflammation. We aimed to examine the modulation of MMP‐9 by calcitriol in TNFα‐treated keratinocytes. The immortalized HaCaT keratinocytes were treated with TNFα in the absence of exogenous growth factors or active ingredients. MMP‐9 production was quantified by gelatin zymography and real‐time RT‐PCR. Activation of signaling cascades was assessed by western blot analysis and DNA‐binding activity of transcription factors was determined by EMSA. Exposure to TNFα markedly increased the protein and mRNA levels of MMP‐9, while pretreatment with calcitriol dose dependently reduced this effect. Employing specific inhibitors we established that the induction of MMP‐9 by TNFα was dependent on the activity of the epidermal growth factor receptor, c‐Jun‐N‐terminal kinase (JNK), NFκB and extracellular signal‐regulated kinase‐1/2. The effect of calcitriol was associated with inhibition of JNK activation and reduction of DNA‐binding activities of the transcription factors activator protein‐1 (AP‐1) and NFκB following treatment with TNFα. By down‐regulating MMP‐9 levels active vitamin D derivatives may attenuate deleterious effects due to excessive TNFα‐induced proteolytic activity associated with cutaneous inflammation. J. Cell. Physiol. 222: 729–737, 2010. © 2009 Wiley‐Liss, Inc.

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Details

Published: Dec 17, 2009
Vol/Issue: 222(3)
Pages: 729-737
License: View

Authors

Cite This Article

K. Bahar‐Shany, A. Ravid, R. Koren (2009). Upregulation of MMP‐9 production by TNFα in keratinocytes and its attenuation by vitamin D. Journal of Cellular Physiology, 222(3), 729-737. https://doi.org/10.1002/jcp.22004

Upregulation of MMP‐9 production by TNFα in keratinocytes and its attenuation by vitamin D

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