Surfactant Protein-D Regulates Soluble CD14 through Matrix Metalloproteinase-12

Senft, Albert P.; Korfhagen, Thomas R.; Whitsett, Jeffrey A.; Shapiro, Steven D.; LeVine, Ann Marie

doi:10.4049/jimmunol.174.8.4953

Cited by 54 publications

(42 citation statements)

References 49 publications

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“…Cell-surface-adhesion molecules, such as syndecan-1, are also shed by soluble and membrane MMPs 31,32 . MMP9 and MMP12 contribute to proteolytic shedding of the lipopolysaccharide (LPS) receptor CD14, and therefore influence innate host defense 33 . TGFβ is another important MMP substrate, the activation of which frequently alters cell migration; for example, MMP9 restrains corneal epithelial migration through the activation of TGFβ 34 .…”

Section: Functions Of Mmp Proteolysismentioning

confidence: 99%

Matrix metalloproteinases and the regulation of tissue remodelling

Page-McCaw

Ewald

Werb

2007

Nat Rev Mol Cell Biol

2,554

2,180

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Matrix metalloproteinases (MMPs) were discovered because of their role in amphibian metamorphosis, yet they have attracted more attention because of their roles in disease. Despite intensive scrutiny in vitro, in cell culture and in animal models, the normal physiological roles of these extracellular proteases have been elusive. Recent studies in mice and flies point to essential roles of MMPs as mediators of change and physical adaptation in tissues, whether developmentally regulated, environmentally induced or disease associated.The founding member of the matrix metalloproteinase (MMP) family, collagenase, was identified in 1962 by Gross and Lapiere, who found that tadpole tails during metamorphosis contained an enzyme that could degrade fibrillar collagen 1,2 . Subsequently, an interstitial collagenase, collagenase-1 or MMP1, was found in diseased skin and synovium 3 . In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775-Ile776 or Gly775-Lys776 in native type I, II or III collagen molecules 3,4 . Further research led to the discovery of a family of structurally related proteinases (23 in human, 24 in mice), now referred to as the MMP family.Interest in MMPs increased in the late 1960s and early 1970s following observations that MMPs are upregulated in diverse human diseases including rheumatoid arthritis and cancer. Importantly, high levels of MMPs often correlated with poor prognosis in human patients (reviewed in REF. 5 ). However, recent clinical data indicate that the relationship between § These authors contributed equally to this paper. Competing interests statementThe authors declare no competing financial interests. DATABASESThe following terms in this article are linked online to: Entrez Genome: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene DmMmp1 | DmMmp2 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMMPs and disease is not simple; for example, increased MMP activity can enhance tumour progression or can inhibit it (reviewed in REF. 6 ). This complex relationship between MMP expression and cancer has increased the basic and clinical interest in understanding MMP function in vivo, but it has also focused attention on MMPs and pathology, and relatively less attention has been focused on the normal roles of these enzymes. MMP proteolysisMMPs are members of the metzincin group of proteases, which are named after the zinc ion and the conserved Met residue at the active site 11,12 . Recent work has generated a unified peptidase nomenclature 13 Functions of MMP proteolysisHistorically, MMPs were thought to function mainly as enzymes that degrade structural components of the ECM. However, MMP proteolysis can create space for cells to migrate, can produce specific substrate-cleavage fragments with independent biological activity, can MMPs in bone modelling and remodellingBone is an important site of ongoing tissue remodelling during development...

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Section: Functions Of Mmp Proteolysismentioning

confidence: 99%

Matrix metalloproteinases and the regulation of tissue remodelling

Page-McCaw

Ewald

Werb

2007

Nat Rev Mol Cell Biol

2,554

2,180

View full text Add to dashboard Cite

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“…Soluble CD14 detected in human sera has been reported to serve as soluble antagonist for monocyte and macrophage activation [17;37]. Soluble CD14 was shown to be released from cell surface by multiple alternative mechanisms including proteolytic processing dependent on MMP12/MMP9 and other MMPs [38], human leukocyte elastase (HLE) [19] and a leukocyte carboxyl/aspartate protease [7]; lipolytic release from the GPI-linker [37] or direct secretion without the GPI moiety [5].…”

Section: Discussionmentioning

confidence: 99%

Soluble hemojuvelin is released by proprotein convertase-mediated cleavage at a conserved polybasic RNRR site

Lin

Nemeth

Goodnough

et al. 2008

Blood Cells, Molecules, and Diseases

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As the principal iron-regulatory hormone, hepcidin plays an important role in systemic iron homeostasis. The regulation of hepcidin expression by iron loading appears to be unexpectedly complex and has attracted much interest. The GPI-linked membrane protein hemojuvelin (GPIhemojuvelin) is an essential upstream regulator of hepcidin expression. A soluble form of hemojuvelin (s-hemojuvelin) exists in blood and acts as antagonist of GPI-hemojuvelin to downregulate hepcidin expression. The release of s-hemojuvelin is negatively regulated by both transferrin-bound iron (holo-Tf) and non-transferrin bound iron (FAC), indicating s-hemojuvelin could be one of the mediators of hepcidin regulation by iron. In this report, we investigate the proteinase involved in the release of s-hemojuvelin and show that s-hemojuvelin is released by a proprotein convertase through the cleavage at a conserved polybasic RNRR site.

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“…These results indicate that factors other than genetic polymorphisms may also be involved in the production of serum sCD14. It has been shown, for example, that CD14 can be proteolytically cleaved from the cell surface to form sCD14 by matrix metalloproteinases (45), which are frequently up-regulated by H. pylori in gastric carcinoma (46 -49).…”

Section: Discussionmentioning

confidence: 99%

Role ofCD14Promoter Polymorphisms inHelicobacter pyloriInfection–Related Gastric Carcinoma

Zhao¹,

Sun²,

Zhang³

et al. 2007

Clinical Cancer Research

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Purpose: Genetic variation in CD14 may affect CD14 expression and susceptibility to Helicobacter pylori infection^related cancers. This study examined functional single nucleotide polymorphisms (SNP) in the CD14 promoter and their associations with risk of developing gastric carcinoma in relation to H. pylori infection. Experimental Design: Thirty individual DNAs were sequenced to identify variants, and the function of the variants was examined by reporter gene assays. Genotypes and haplotypes were analyzed in 470 patients and 470 controls, and odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression. Serologic H. pylori antibody and soluble CD14 (sCD14) levels were measured by ELISA. Results: Two SNPs (À651C>T and À260C>T) were identified, of which the À260CT and À260TT genotypes were associated with elevated risk of gastric carcinoma (OR, 1.77; 95% CI, 1.09-2.85 and OR, 1.95; 95% CI, 1.20-3.16, respectively). Haplotype analysis suggested a synergistic effect of the two SNPs (OR for the T À651 -T À260 haplotype, 3.39 versus OR for the C À651 -T À260 haplotype, 1.45; P = 0.02), which is consistent with reporter gene assays. A multiplicative joint effect between H. pylori infection and À260C>T polymorphism was observed (OR for the presence of both À260TTgenotype and H. pylori infection, 4.03; 95% CI, 1.80-9.04). Patients had significantly higher sCD14 than controls (1,866 F 2,535 ng/mL versus1,343 F 2,119 ng/mL; P < 0.001), and this difference was associated with the CD14 À260 polymorphism and H. pylori infection. Conclusions: Functional polymorphism in CD14 is associated with greater risk of H. pylorir elated gastric carcinoma, which might be mediated by elevated sCD14.

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Surfactant Protein-D Regulates Soluble CD14 through Matrix Metalloproteinase-12

Cited by 54 publications

References 49 publications

Matrix metalloproteinases and the regulation of tissue remodelling

Matrix metalloproteinases and the regulation of tissue remodelling

Soluble hemojuvelin is released by proprotein convertase-mediated cleavage at a conserved polybasic RNRR site

Role ofCD14Promoter Polymorphisms inHelicobacter pyloriInfection–Related Gastric Carcinoma

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