Defective production of soluble HLA-G molecules by peripheral blood monocytes in patients with asthma

Rizzo, Roberta; Mapp, C. E.; Melchiorri, Loredana; Maestrelli, Piero; Visentin, Annalisa; Ferretti, Stefano; Bononi, Ilaria; Miotto, Deborah; Baricordi, Olavio R.

doi:10.1016/j.jaci.2004.11.031

Cited by 63 publications

(75 citation statements)

References 47 publications

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“…Of the different forms of HLA-G described, expression in the lung was limited to the soluble isoform (G1). Differing from other HLA molecules, HLA-G is a major histocompatibility complex class 1 molecule involved in regulating the type and level of chronic forms of inflammation and specifically the Th1/Th2 T-cell balance [95].…”

Section: Disease Linkage Analysis and Positional Cloningmentioning

confidence: 99%

Local genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanisms

Holgate¹,

Davies²,

Powell³

et al. 2007

Eur Respir J

120

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While asthma is an inflammatory disorder of the airways usually associated with atopy, an important additional component is involvement of the epithelium and underlying mesenchyme acting as a trophic unit (EMTU).In addition to allergens, a wide range of environmental factors interact with the EMTU, such as virus infections, environmental tobacco smoke and pollutants, to initiate tissue damage and aberrant repair responses that are translated into remodelling of the airways. While candidate gene association studies have revealed polymorphic variants that influence asthmatic inflammation, positional cloning of previously unknown genes is identifying a high proportion of novel genes in the EMTU.Dipeptidyl peptidase (DPP) 10 and disintegrin and metalloproteinase (ADAM)33 are newly identified genes strongly associated with asthma that are preferentially expressed in the airway epithelium and underlying mesenchyme, respectively.Also of increasing importance is the recognition that genes associated with asthma and atopy have important interactions with the environment through epigenetic mechanisms that influence their expression. This type of research will not only identify biomarkers of different types of asthma across the full range of phenotypic expression, but will also identify novel therapeutic targets that could influence the natural history of the heterogenes lung disease.

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Section: Disease Linkage Analysis and Positional Cloningmentioning

confidence: 99%

Local genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanisms

Holgate¹,

Davies²,

Powell³

et al. 2007

Eur Respir J

120

View full text Add to dashboard Cite

show abstract

“…It is well described that the extended HLA-haplotype, including the HLA-DRB1 * 01/ * 04 combination, is associated with cardiovascular disease and mortality (32). Of interest, an association between HLA-G polymorphisms and other chronic inflammatory disorders, such as inflammatory bowel disease (33,34), asthma (35,36) and multiple sclerosis (37)(38)(39), has been repeatedly reported. Besides the potential role played by HLA-G in inflammation and immunity (15), there is evidence to suggest that this molecule may also modulate endothelial cell activity (40,41).…”

Section: Discussionmentioning

confidence: 99%

Association between two polymorphisms in the HLA-G gene and angiographic coronary artery disease

et al. 2012

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“…In organ transplantation there is a clear correlation between increased sHLA-G serum level and a diminished number of rejection episodes (19). Moreover, in autoimmune diseases nonactive clinical conditions in relapsingremitting multiple sclerosis patients correlates with the presence of sHLA-G in cerebrospinal fluid (20), while impairment in the production of these antiinflammatory molecules is related to persistence of severe asthma (21). Finally, high HLA-G expression in rheumatoid arthritis and ulcerative colitis suggests that this molecule might have a broader involvement in inflammation (54,55).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, increased sHLA-G levels in cerebrospinal fluids have been associated with the absence of clinical activity in multiple sclerosis (20), while in solid organ transplantation high sHLA-G serum concentrations were detected in patients with a reduced number of rejection episodes (19). A reduced sHLA-G production was suggested to play a role in the persistence of inflammatory conditions in asthma (21). However, HLA-G expression may also mediate negative clinical outcome in cancer where increased membrane-bound or sHLA-G molecules have been associated with poor prognosis (17).…”

mentioning

confidence: 99%

Extracellular ATP Acting at the P2X7 Receptor Inhibits Secretion of Soluble HLA-G from Human Monocytes

Rizzo¹,

Ferrari

Melchiorri³

et al. 2009

The Journal of Immunology

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Bacterial LPS induces the release of ATP from immune cells. Accruing evidence suggests that extracellular ATP participates in the inflammatory response as a proinflammatory mediator by activating the inflammasome complex, inducing secretion of cytokines (IL-1, IL-18) and cell damaging agents such as oxygen radicals, cationic proteins, and metalloproteases. It is not known whether ATP can also act as a proinflammatory mediator by inhibiting production of molecules down-modulating the immune response. Here, we show that extracellular ATP impairs in an IL-10-dependent fashion the expression of the tolerogenic soluble and membrane-bound HLA-G Ag in human monocytes. The effect of ATP was mimicked by BzATP (3′-O-(4-benzoyl)benzoyl-ATP) and greatly reduced by pretreatment with oATP (periodate-oxidized ATP), KN-62 (1-[N,O-bis(5-isoquinoline-sulfonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine), and an anti-P2X7 mAb, thus pointing to a specific role of the P2X7 receptor. The effect of ATP was time- and dose-dependent and was not due to a decrease in expression of IL-10 receptor. Inhibition by ATP was reverted by supplementation of culture medium with exogenous IL-10. Due to the well-known immunosuppressive activity of IL-10 and soluble HLA-G, this novel effect of ATP might be relevant for the pathophysiology and therapy of inflammatory disorders.

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Defective production of soluble HLA-G molecules by peripheral blood monocytes in patients with asthma

Cited by 63 publications

References 47 publications

Local genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanisms

Local genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanisms

Association between two polymorphisms in the HLA-G gene and angiographic coronary artery disease

Extracellular ATP Acting at the P2X7 Receptor Inhibits Secretion of Soluble HLA-G from Human Monocytes

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