Mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation

Filippo, Katia De; Dudeck, Anne; Hasenberg, Mike; Nye, Emma; Rooijen, Nico van; Hartmann, Karin; Gunzer, Matthias; Roers, Axel; Hogg, Nancy

doi:10.1182/blood-2013-02-486217

Cited by 702 publications

(624 citation statements)

References 49 publications

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“…Interestingly, these investigators found that the production of CXCL1 from TRAMP-G2LG cancer cells reached ∼4 ng/ml, similar to the concentration of CXCL1 that inhibited ASMC migration in our study. These results suggest that, although known as a mediator of cell chemotaxis (16,17), at specific concentrations CXCL1 may act as a negative regulator of cell migration/invasion both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 83%

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CXCL1 Inhibits Airway Smooth Muscle Cell Migration through the Decoy Receptor Duffy Antigen Receptor for Chemokines

Al-Alwan

Chang

Rousseau

et al. 2014

The Journal of Immunology

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Airway smooth muscle cell (ASMC) migration is an important mechanism postulated to play a role in airway remodeling in asthma. CXCL1 chemokine has been linked to tissue growth and metastasis. In this study, we present a detailed examination of the inhibitory effect of CXCL1 on human primary ASMC migration and the role of the decoy receptor, Duffy AgR for chemokines (DARC), in this inhibition. Western blots and pathway inhibitors showed that this phenomenon was mediated by activation of the ERK-1/2 MAPK pathway, but not p38 MAPK or PI3K, suggesting a biased selection in the signaling mechanism. Despite being known as a nonsignaling receptor, small interference RNA knockdown of DARC showed that ERK-1/2 MAPK activation was significantly dependent on DARC functionality, which, in turn, was dependent on the presence of heat shock protein 90 subunit α. Interestingly, DARC- or heat shock protein 90 subunit α–deficient ASMCs responded to CXCL1 stimulation by enhancing p38 MAPK activation and ASMC migration through the CXCR2 receptor. In conclusion, we demonstrated DARC’s ability to facilitate CXCL1 inhibition of ASMC migration through modulation of the ERK-1/2 MAPK–signaling pathway.

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Section: Discussionmentioning

confidence: 83%

“…Although primarily known as a potent inducer of neutrophil chemotaxis (16), CXCL1 was shown to induce cancer cell invasion (17) and endothelial (18) and epithelial cell migration (19). CXCL1 facilitates its signaling by binding to its putative receptor, the chemokine receptor CXCR2, although it also was found to bind to CXCR1, albeit with lower affinity (20).…”

mentioning

confidence: 99%

CXCL1 Inhibits Airway Smooth Muscle Cell Migration through the Decoy Receptor Duffy Antigen Receptor for Chemokines

Al-Alwan

Chang

Rousseau

et al. 2014

The Journal of Immunology

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“…The most notable changes in the cells treated with the combination of LG268 and LPS compared with LPS alone were a 3-fold downregulation of CSF3 and a 2.5-fold decrease of CXCL2 and IL1b mRNA expression. These cytokines play important roles in inflammation: CSF3 in the production and function of granulocytes (30), CXCL2 in the recruitment of neutrophils (31), and IL1b in promoting the infiltration of inflammatory myeloid cells and in angiogenesis (32,33). A complete list of the inflammatory cytokines, chemokines, and their receptors that showed any detectable changes in the panel of 440 genes following treatment with LG268 are listed in Supplementary Table S1.…”

Section: Resultsmentioning

confidence: 99%

The Rexinoids LG100268 and LG101506 Inhibit Inflammation and Suppress Lung Carcinogenesis in A/J Mice

Cao

Royce

Risingsong

et al. 2016

Cancer Prevention Research

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LG101506 was originally synthesized to overcome some of the undesirable side effects of rexinoids. We compared the anticarcinogenic action of LG101506 and LG100268 and for the first time showed that both drugs are useful for prevention of lung cancer in A/J mice. These molecules markedly reduced tumor number, tumor size, and total tumor burden, when chronically administered to A/J mice that had been initiated with the mutagenic carcinogen, vinyl carbamate. Moreover, LG100268 synergized with the histone deacetylase inhibitor, vorinostat, for prevention of experimental lung cancer and enhanced the effect of carboplatin/paclitaxel for treatment of experimental lung cancer. Both rexinoids diminished the percentage of high-grade, highly malignant adenocarcinomas found at autopsy. In cell culture studies, the rexinoids exhibited potent anti-inflammatory properties at nanoMolar concentrations. These drugs suppressed the ability of lipopolysaccharide to stimulate the synthesis and secretion of nitric oxide and inflammatory cytokines and chemokines, such as IL6, IL1b, CXCL2, and CSF3, in macrophage-like RAW264.7 cells. The present results suggest that LG100268, LG101506, or a related rexinoid may have useful clinical applications in the field of oncology. Cancer Prev Res; 9(1);

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“…In addition, the expression of CXCL2, the chemokine mainly responsible for recruiting neutrophils, 13,14 was found to be increased in the skin lesion both at the early and late stages (Figures 5a and b). Accordingly, there was significantly increased numbers of neutrophils in the lesional skin of the patients with SSc compared with the normal skin of the health control.…”

Section: Discussionmentioning

confidence: 97%

“…In addition, the expressions of chemokines CXCL2 and CCL17 were shown to be induced in the skin lesion following implantation of minipumps with BLM (Figure 5b), which strongly supported the cellular infiltration of neutrophils and T cells in the skin lesion according to their preferential chemotactic ability. [13][14][15][16] Delivery of BLM by Skin-Embedded Osmotic Minipumps Induces Interstitial Lung Disease-Like Manifestation SSc is a systemic autoimmune disease with multiple organs involved, and ILD is one of the most significant complications in SSc. TGF-b1 is widely considered to have a central role in fibrosis.…”

Section: Delivery Of Blm By Skin-embedded Osmotic Minipumpsmentioning

confidence: 99%

A modified murine model of systemic sclerosis: bleomycin given by pump infusion induced skin and pulmonary inflammation and fibrosis

Liang

Zou

et al. 2015

Laboratory Investigation

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Daily subcutaneous (sc) injection of bleomycin (BLM) causes dermal fibrosis but rarely causes lung changes in mice. There are also significant disadvantages to this traditional model for systemic sclerosis, including a variable distribution of lesions and a requirement for repetitive procedures. The present study was undertaken to develop a convenient method of BLM administration that yields stable dermal inflammation and fibrosis with extensive and reproducible interstitial lung disease (ILD) in mice. Osmotic minipumps containing BLM (150 mg/kg) or saline were implanted sc in C57BL/6 mice and the drug was delivered as a continuous infusion over 1B4 weeks. The time course of morphological features, collagen content, and pro-inflammatory cytokine expression in the skin and the lungs were analyzed. Pathological examination demonstrated dominant inflammatory infiltrates at week 1 and significant fibrosis at week 4. Decreased microvessel density and increased myofibroblast counts were observed in the skin of BLM-treated mice at week 4. In addition, there were obvious increases in dermal infiltration of CD45 þ leukocytes, including F4/80 þ macrophages, Gr-1 þ neutrophils, and CD3 þ T lymphocytes in BLM-treated mice. IL-1b, IL-4, and CXCL2 transcripts were continually upregulated by BLM in the skin and lung tissues. In addition, lungs from BLM-treated mice showed significant inflammatory infiltrates and confluent subpleural fibrosis at week 4. In conclusion, this modified murine model for drug-induced systemic inflammation and fibrosis uses a single procedure and provides reproducible skin and lung lesions, mimicking human systemic sclerosis (SSc) with ILD-like manifestation.

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Mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation

Abstract: Key Points Mast cells contribute to early neutrophil recruitment. Mast cells and macrophages both make CXCL1 and CXCL2.

Cited by 702 publications

References 49 publications

CXCL1 Inhibits Airway Smooth Muscle Cell Migration through the Decoy Receptor Duffy Antigen Receptor for Chemokines

CXCL1 Inhibits Airway Smooth Muscle Cell Migration through the Decoy Receptor Duffy Antigen Receptor for Chemokines

The Rexinoids LG100268 and LG101506 Inhibit Inflammation and Suppress Lung Carcinogenesis in A/J Mice

A modified murine model of systemic sclerosis: bleomycin given by pump infusion induced skin and pulmonary inflammation and fibrosis

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