Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1

Johnston, Brent; Burns, Alan R.; Suematsu, Makoto; Issekutz, Thomas B.; Woodman, Richard C.; Kubes, Paul

doi:10.1172/jci5208

Cited by 183 publications

(150 citation statements)

References 44 publications

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“…6). It was remarked that many genes are known to have their involvements in inflammatory or coagulation response such as Ccl2, Ccl7, Cxcl2, F2r, F3 and Crp among annotated genes (Bharadwaj et al, 1999;Hsu et al, 2006;Johnston et al, 1999). This observation concurred with previously reported clinical effects of statins on inflammation or coagulation (Dols et al, 2009, Maitlandvan der Zee et al, 2009).…”

Section: Pcr Verification Of Expression Level Of the Putative Indicatsupporting

confidence: 81%

Gene Expression Analysis for Statin-induced Cytotoxicity from Rat Primary Hepatocytes

Ko¹,

Ahn²,

Shin³

et al. 2010

Genomics & Informatics

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Statins are competitive inhibitors of hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase and used most frequently to reduce plasma cholesterol levels and to decrease cardiovascular events. However, statins also have been reported to have undesirable side effects such as myotoxicity and hepatotoxicity associated with their intrinsic efficacy mechanisms. Clinical studies recurrently reported that statin therapy elevated the level of liver enzymes such as ALT and AST in patients suggesting possible liver toxicity due to statins. This observation has been drawn great attention since statins are the most prescribed drugs and statin-therapy was extended to a larger number of high-risk patients. Here we employed rat primary hepatocytes and microarray technique to understand underlying mechanism responsible for statin-induced liver toxicity on cell level. We isolated genes whose expressions were commonly modulated by statin treatments and examined their biological functions. It is of interest that those genes have function related to response to stress in particular immunity and defense in cells. Our study provided the basic information on cellular mechanism of statin-induced cytotoxicity and may serve for finding indicator genes of statin -induced toxicity in rat primary hepatocytes.

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Section: Pcr Verification Of Expression Level Of the Putative Indicatsupporting

confidence: 81%

Gene Expression Analysis for Statin-induced Cytotoxicity from Rat Primary Hepatocytes

Ko¹,

Ahn²,

Shin³

et al. 2010

Genomics & Informatics

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“…This defect was not a consequence of lowered circulating neutrophil numbers, as previous studies have shown that CCR2 Ϫ/Ϫ mice have a normal compliment of circulating polymorphonuclear cells (15). The paucity of neutrophils may have been due to decreases in KC levels or a direct consequence of neutrophils lacking the ability to respond to MCP-1, which will promote the chemotaxis of neutrophils during acute (34) and chronic inflammatory conditions (12). Thus, these findings suggest that CCR2 has a major role in the recruitment of neutrophils during an intrapulmonary challenge with A. fumigatus conidia, and the paucity of neutrophils may explain the persistence of A. fumigatus in the airways of CCR2 Ϫ/Ϫ mice.…”

Section: Discussionmentioning

confidence: 82%

Enhanced Pulmonary Allergic Responses toAspergillusin CCR2−/− Mice

Blease¹,

Mehrad

Standiford

et al. 2000

The Journal of Immunology

147

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Allergic responses to Aspergillus species exacerbate asthma and cystic fibrosis. The natural defense against live Aspergillus fumigatus spores or conidia depends on the recruitment and activation of mononuclear and polymorphonuclear leukocytes, events that are dependent on chemotactic cytokines. In this study, we explored the relative contribution of the monocyte chemoattractant protein-1 receptor, CCR2, in the pulmonary response to A. fumigatus conidia. Following sensitization to soluble A. fumigatus Ags, mice lacking CCR2 due to targeted deletion were markedly more susceptible to the injurious effects of an intrapulmonary challenge with live conidia compared with mice that expressed CCR2 or CCR2+/+. CCR2−/− mice exhibited a major defect in the recruitment of polymorphonuclear cells, but these mice also had significantly more eosinophils and lymphocytes in bronchoalveolar lavage samples. CCR2−/− mice also had significant increases in serum levels of total IgE and whole lung levels of IL-5, IL-13, eotaxin, and RANTES compared with CCR2+/+ mice. Airway inflammation, hyper-responsiveness to spasmogens, and subepithelial fibrosis were significantly enhanced in CCR2−/− mice compared with CCR2+/+ mice after the conidia challenge. Thus, these findings demonstrate that CCR2 plays an important role in the immune response against A. fumigatus, thereby limiting the allergic airway inflammatory and remodeling responses to this fungus.

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“…MCP-1 can contribute to neutrophil recruitment by acting on monocytes and macrophages (31) and in some settings by activating neutrophils directly (44,45), suggesting that diminished MCP-1 may also be a factor in the decreased neutrophil recruitment of TM mice. In contrast, LIX concentrations were unaffected by interruption of TNF-␣ and IL-1 signaling, indicating that LIX has distinct regulation from the chemokines KC, MIP-2, and MCP-1 during pneumococcal pneumonia.…”

Section: Discussionmentioning

confidence: 99%

Lung NF-κB Activation and Neutrophil Recruitment Require IL-1 and TNF Receptor Signaling during Pneumococcal Pneumonia

Jones

Simms

Lupa

et al. 2005

The Journal of Immunology

143

126

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Pulmonary inflammation is an essential component of the host defense against Streptococcus pneumoniae infection of the lungs. The early response cytokines, TNF-α and IL-1, are rapidly induced upon microbial exposure. Mice deficient in all TNF- and IL-1-dependent signaling receptors were used to determine the roles of these cytokines during pneumococcal pneumonia. The deficiency of signaling receptors for TNF and IL-1 decreased bacterial clearance. Neutrophil recruitment to alveolar air spaces was impaired by receptor deficiency, as was pulmonary expression of the neutrophil chemokines KC and MIP-2. Because NF-κB mediates the expression of both chemokines, we assessed NF-κB activation in the lungs. During pneumococcal pneumonia, NF-κB proteins translocate to the nucleus and activate gene expression; these functions were largely abrogated by the deficiency of receptors for TNF-α and IL-1. Thus, the combined deficiency of TNF and IL-1 signaling reduces innate immune responses to S. pneumoniae in the lungs, probably due to essential roles for these receptors in activating NF-κB.

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Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1

Cited by 183 publications

References 44 publications

Gene Expression Analysis for Statin-induced Cytotoxicity from Rat Primary Hepatocytes

Gene Expression Analysis for Statin-induced Cytotoxicity from Rat Primary Hepatocytes

Enhanced Pulmonary Allergic Responses toAspergillusin CCR2−/− Mice

Lung NF-κB Activation and Neutrophil Recruitment Require IL-1 and TNF Receptor Signaling during Pneumococcal Pneumonia

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