CXCR2 antagonists for the treatment of pulmonary disease

Chapman, Richard W.; Phillips, Jonathan E.; Hipkin, R. William; Curran, Aidan K.; Lundell, Daniel; Fine, Jay S.

doi:10.1016/j.pharmthera.2008.10.005

Cited by 194 publications

(189 citation statements)

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“…CXCR2 and its chemokine ligands genotypes are involved in a wide range of acute and chronic inflammatory diseases, including acute respiratory distress syndrome (Kurdowska et al, 2002), rheumatoid arthritis (Erdem et al, 2005;Lally et al, 2005), psoriasis (Reich et al, 2001), inflammatory bowel disease (Banks et al, 2003), chronic obstructive pulmonary disease and asthma (Keatings et al, 1996;Beeh et al, 2003;Chapman et al, 2009), aggressive cancer (Snoussi et al, 2010), cystic fibrosis (Koller et al, 1997), and atherosclerosis (Bizzarri et al, 2006). However, whether different genotypes of the genes coding for these cytokines are involved in the susceptibility to opportunistic infections among HIV patients is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…Of the different subclasses of chemokines, the CXC family of chemokines are particularly important in the initiation and amplification of inflammatory diseases (Chapman et al, 2009) such as tuberculosis (TB) (Otsuka et al, 2005), diarrhea (Jiang et al, 2003), chest pain (Stadtmann and Zarbock, 2012), and loss of appetite, which eventually lead to unexplained weight loss. The CXCR2 chemokine receptor is a glycoprotein-coupled receptor found primarily on the surface of leukocytes and binds to interleukin-8 (IL-8) with high affinity.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…There is a growing body of evidence indicating that CXCR2 plays an important role in pulmonary disease (Chapman et al, 2009). Several pharmaceutical companies have identified potent and selective CXCR2 candidates that have now advanced into clinical trials (Chapman et al, 2009). Examining the genetic variation associated with disease will increase the understanding of why some patients die in a short period of time while others remain healthy for longer periods, even if both have the same infection.…”

Section: Introductionmentioning

confidence: 99%

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Distribution of CXCR2 +1208 T/C gene polymorphisms in relation to opportunistic infections among HIV-infected patients in Limpopo Province, South Africa

Samie¹,

Dzhivhuho²,

Nangammbi³

2014

Genet. Mol. Res.

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ABSTRACT. Interleukin 8 (IL-8) is a chemokine produced by macrophages and other cell types, including epithelial cells, and its receptor is CXCR2. IL-8 plays an important role in the initiation and amplification of inflammatory diseases, including opportunistic infections. With the advent of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome, opportunistic infections have become major health concerns. However, the role of host genetics on the occurrence of these infections has not been clearly defined. In this study, genomic DNA was extracted from 185 HIVinfected individuals in the Limpopo Province, South Africa. Allelespecific polymerase chain reaction was used to genotype the CXCR2 +1208 T/C gene. Genotypes CC, TT, and TC were associated with chest pains, frequent headaches, loss of weight, diarrhea, and loss of appetite among HIV patients. A significant association between the CC CXCR2 gene polymorphism among HIV patients genotype and chest pains was found (P = 0.035). The TC genotype was associated with loss of appetite (P = 0.044) and chest pains (P = 0.042). A weak association between diarrhea and the TT genotype was found (P = 0.082). No association was observed between tuberculosis and the genotypes. Immunological characteristics, such as viral load and CD4 count, were not significantly associated with the genotypes. The results of the present study suggest that carriers of the TC genotype are more susceptible to chest pain, but that this genotype confers a protective effect against loss of appetite. The CC genotype was found to confer protection against chest pain but appeared to increase susceptibility to headaches. Further studies using larger samples are necessary to confirm these results.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Distribution of CXCR2 +1208 T/C gene polymorphisms in relation to opportunistic infections among HIV-infected patients in Limpopo Province, South Africa

Samie¹,

Dzhivhuho²,

Nangammbi³

2014

Genet. Mol. Res.

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show abstract

“…For example, anti-CXCR2 therapy could reduce neutrophil recruitment and keep macrophage phagocytic function active with the neutrophil burden in the airways of patients with chronic obstructive pulmonary disease or cystic fibrosis [15]. Recent data suggest that CXCR2 also mediates the formation of neutrophil extracellular traps and DNA fibers coated with antimicrobial proteins that serve an important function in host defense.…”

Section: Editorialmentioning

confidence: 99%