Activation of latent transforming growth factor-beta1 by nitric oxide in macrophages: role of soluble guanylate cyclase and MAP kinases.
The inducible nitric oxide (NO) synthase and the cytokine transforming growth factor-[beta]1 (TGF-[beta]1), both central modulators of wound healing, interact reciprocally: TGF-[beta]1 generally suppresses iNOS expression, while NO can induce and activate latent TGF-[beta]1. We have shown that chemi...
| Publicado en: | Wound Repair & Regeneration Vol. 17; no. 4; pp. 578 - 589 |
|---|---|
| Autores principales: | , , , , , , , , , |
| Formato: | equations & formulas pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Jul/Aug2009
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105388865&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105388865 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 10671927 DPV jtl: Wound Repair & Regeneration issn: 10671927 maglogo: Y pubinfo: dt: Jul/Aug2009 vid: 17 iid: 4 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 105388865 105388865 2010350262 10.1111/j.1524-475x.2009.00509.x 105388865 ppf: 578 ppct: 11 formats: fmt: @attributes: type: P tig: atl: Activation of latent transforming growth factor-beta1 by nitric oxide in macrophages: role of soluble guanylate cyclase and MAP kinases. aug: au: Metukuri MR Namas R Gladstone C Clermont T Jefferson B Barclay D Hermus L Billiar TR Zamora R Vodovotz Y affil: Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania sug: subj: Growth Substances Metabolism Macrophages Physiology Nitric Oxide Metabolism Transforming Growth Factor beta Blotting, Northern Blotting, Western Data Analysis Software Descriptive Statistics Fisher's Exact Test Funding Source Immunohistochemistry In Vitro Studies Mann-Whitney U Test One-Way Analysis of Variance Post Hoc Analysis T-Tests Tissue Culture Techniques Wound Healing Physiology Human ab: The inducible nitric oxide (NO) synthase and the cytokine transforming growth factor-[beta]1 (TGF-[beta]1), both central modulators of wound healing, interact reciprocally: TGF-[beta]1 generally suppresses iNOS expression, while NO can induce and activate latent TGF-[beta]1. We have shown that chemical NO activates recombinant human latent TGF-[beta]1 by S-nitrosation of the latency-associated peptide (LAP), a cleaved portion of pro-TGF-[beta]1 that maintains TGF-[beta]1 in a biologically-inactive state. We hypothesized that cell-associated TGF-[beta]1 could be activated by NO via known NO-inducible signaling pathways (soluble guanylate cyclase [sGC] and mitogen-activated protein [MAP] kinases). Treatment of mouse RAW 264.7 macrophage-like cells with the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) led to a dose- and time-dependent increase in cell-associated active and latent TGF-[beta]1, as assessed by quantitative immunocytochemistry for active TGF-[beta]1 vs. LAP and partially validated by western blot analysis. Treatment with the sGC inhibitor 1,H-[1,2,4]oxadiazole[4,3-a]quinoxalon-1-one (ODQ) reduced both active and latent TGF-[beta]1 dose-dependently. SNAP, in the presence or absence of ODQ or the MAP kinase inhibitors, did not affect steady-state TGF-[beta]1 mRNA levels. Treatment with inhibitors specific for JNK1/2, ERK1/2, and p38 MAP kinases suppressed SNAP-induced active and latent TGF-[beta]1. Treatment with the cell-permeable cGMP analog 8-Br-cGMP increased both active and latent TGF-[beta]1. However, TGF-[beta]1 activation induced by 8-Br-cGMP was not blocked by MAP kinase inhibitors. Our findings suggest that NO activates latent TGF-[beta]1 via activation of sGC and generation of cGMP and separately via MAP kinase activation, and may shed insight into the mechanisms by which both cGMP production and MAP kinase activation enhance wound healing. pubtype: Academic Journal doctype: equations & formulas pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|