CXCL1: Gene, Promoter, Regulation of Expression, mRNA Stability, Regulation of Activity in the Intercellular Space

Korbecki, Jan; Barczak, Katarzyna; Gutowska, Izabela; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

doi:10.3390/ijms23020792

Cited by 71 publications

(44 citation statements)

References 219 publications

(338 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present study identifies specific chemokines whose expression is acutely repressed by STAT3, thereby limiting the development of inflammation. CXCL1, CXCL10, and CCL2 are all induced by TNF through activation of NF‐κB in various cell types 48–50 . Here, we show that in MEFs TNF represses the expression of these chemokines through TNF‐induced expression of A20/Tnfaip3, and that this pathway is also highly STAT3 dependent.…”

Section: Discussionmentioning

confidence: 59%

“…CXCL1, CXCL10, and CCL2 are all induced by TNF through activation of NF‐κB in various cell types. 48 , 49 , 50 Here, we show that in MEFs TNF represses the expression of these chemokines through TNF‐induced expression of A20/Tnfaip3, and that this pathway is also highly STAT3 dependent. We suggest that NF‐κB and STAT3 cooperate to regulate A20/Tnfaip3 expression, which is supported by the finding that CXCL1, CXCL10, and CCL2 production is increased by TNF in STAT3 KO MEFs relative to WT MEFs and that enforced expression of A20/Tnfaip3 in STAT3 KO MEFs suppresses the levels of these chemokines.…”

Section: Discussionmentioning

confidence: 64%

See 1 more Smart Citation

STAT3 regulates inflammatory cytokine production downstream of TNFR1 by inducing expression of TNFAIP3/A20

Antonia

Karelehto

Toriguchi

et al. 2022

J Cellular Molecular Medi

View full text Add to dashboard Cite

Tumour Necrosis Factor (TNF) potently induces a transient inflammatory response that must be downregulated once any invasive stimulus has resolved. Yet, how TNF‐induced inflammation is shut down in normal cells is incompletely understood. The present study shows that STAT3 was activated in mouse embryo fibroblasts (MEFs) by treatment with TNF or an agonist antibody to TNFR1. STAT3 activation was inhibited by pharmacological inhibition of the Jak2 tyrosine kinase that associates with TNFR1. To identify STAT3 target genes, global transcriptome analysis by RNA sequencing was performed in wild‐type MEFs and MEFs from STAT3 knockout (STAT3 KO ) mice that were stimulated with TNF, and the results were validated at the protein level by using multiplex cytokine assays and immunoblotting. After TNF stimulation, STAT3 KO MEFs showed greater gene and protein induction of the inflammatory chemokines Ccl2, Cxcl1 and Cxcl10 than WT MEFs. These observations show that, by activating STAT3, TNF selectively modulates expression of a cohort of chemokines that promote inflammation. The greater induction by TNF of chemokines in STAT3 KO than WT MEFs suggested that TNF induced an inhibitory protein in WT MEFs. Consistent with this possibility, STAT3 activation by TNFR1 increased the expression of Tnfaip3/A20, a ubiquitin modifying enzyme that inhibits inflammation, in WT MEFs but not in STAT3 KO MEFs. Moreover, enforced expression of Tnfaip3/A20 in STAT3 KO MEFs suppressed proinflammatory chemokine expression induced by TNF. Our observations identify Tnfaip3/A20 as a new downstream target for STAT3 which limits the induction of Ccl2, Cxcl1 and Cxcl10 and inflammation induced by TNF.

show abstract

Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 64%

STAT3 regulates inflammatory cytokine production downstream of TNFR1 by inducing expression of TNFAIP3/A20

Antonia

Karelehto

Toriguchi

et al. 2022

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…C–X–C motif chemokine ligand 1 (CXCL1)/GRO is a chemotactic cytokine engaged in the development of many inflammatory disorders, although its significance has been most extensively evaluated in tumors. CXCL1 serves as potent regulator of: neutrophil recruitment, angiogenesis and wound healing [ 23 , 24 ]. Its receptors include, inter alia, CXCR2 (CXC motifs receptors 2) that is mainly expressed on neutrophils, but can be also detected on: monocytes, NK cells, mast cells, basophils, cytotoxic T and endothelium.…”

Section: Discussionmentioning

confidence: 99%

Cytokines and chemokines multiplex analysis in patients with low disease activity rheumatoid arthritis

et al. 2022

View full text Add to dashboard Cite

Rheumatoid arthritis is a severe chronic autoimmune disorder that results from pathological activation of immune cells and altered cytokine/chemokine network. The aim of our study was to evaluate concentrations of chosen cytokines and chemokines in blood sera and synovial fluid samples isolated from low disease activity rheumatoid arthritis (RA) patients and osteoarthritis (OA) sufferers. Blood sera and synovial fluid samples have been obtained from 24 OA and 14 RA patients. Cytokines/chemokines levels have been determined using a Milliplex® Map 38-plex human cytokine/chemokine magnetic bead-based panel (Merck Millipore, Germany) and Luminex® MAGPIX® platform (Luminex USA). Low disease activity RA patients showed altered concentration of numerous cytokine/chemokine when compared to OA controls—they were characterized by, inter alia, increased: eotaxin/CCL11 (p = 0.037), GRO/CXCL1 (p = 0.037), IL-2 (p = 0.013), IL-4 (p = 0.017), IL-7 (p = 0.003), IL-8 (p = 0.0007) and GM-CSF (p = 0.037) serum levels, whilst MDC/CCL22 concentration was decreased in this group (p = 0.034). Eotaxin/CCL11 (p = 0.001), GRO/CXCL1 (p = 0.041), IL-10 (p = 0.003), GM-CSF (p = 0.01), IL-1RA (p = 0.0005) and VEGF (p = 0.01) concentrations in synovial fluid of RA females were also increased. Even with low disease activity score, RA patients exhibited increased concentrations of cytokines with pro- and anti-inflammatory activities, as well as numerous chemokines, growth factors and regulators of angiogenesis. Surprisingly, RA subjects also shown decreased concentration of CCL22 chemokine. The attempt to restore cytokine balance and tolerogenic environment is ineffective in RA sufferers even with good disease management. Distinguished factors could serve as possible indicators of disease progression even in low disease activity patients.

show abstract

“…Another reason is that patients with less severe organ damage were examined because of the exclusion criteria. CXCL1 is one of the most important chemokines, which is involved in the pathogenesis of many inflammatory diseases; CXCL1 is upregulated in inflammatory responses and induces angiogenesis and recruits neutrophils [ 20 ]. Whereas the utility of bronchoalveolar lavage (BAL) in the evaluation of SSc-ILD remains controversial, fractional analysis of BAL (FBAL), which is a technique that can analyze small airways and alveolar compartments separately, has proven informative in other ILDs [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Serum C-X-C Chemokine Ligand 1 Levels in Patients with Systemic Sclerosis: Relationship of Clinical and Laboratory Observations to Anti-CD20 Monoclonal Antibody Administration

Kawanabe

Yoshizaki

Matsuda

et al. 2022

Life

View full text Add to dashboard Cite

Objectives: To determine whether C-X-C chemokine ligand 1 (CXCL1), which is a potent neutrophil chemoattractant and activator that plays important role in inflammation, is elevated in patients with systemic sclerosis (SSc) and whether it is associated with the clinical features and disease activity of patients with SSc. In addition, to determine whether the changes in serum CXCL1 levels before and after treatment correlate with changes in disease activity in SSc patients who received an anti-CD20 monoclonal antibody drug. Patients and method: We examined patient serum collected in the DesiReS trial, which was a double-blind, parallel-group, randomized, placebo-controlled, multicenter, phase II clinical trial. In the trial, patients were randomly allocated to the drug or placebo group and received 375 mg/m2 of an anti-CD20 antibody, rituximab, or placebo once a week for four weeks. We obtained serum samples from 47 patients administered at our hospital, including 3 males and 44 females, the median age of 48 years, range 27–71 years, with 42 diffuse cutaneous SSc and 5 with limited cutaneous SSc. Serum CXCL1 levels were measured using multiplex immunoassay in patient serum before and 24 weeks after administration and also in serum from 33 healthy controls. Results: Serum CXCL1 levels were significantly higher in SSc patients (mean 25.70 ng/mL; 95% confidence interval (CI) 18.35–33.05 ng/mL) than in the healthy controls (15.61 ng/mL; 95% CI 9.73–21.51 ng/mL). In addition, SSc patients with elevated CXCL1 levels had a significantly higher percentage of area occupied with interstitial shadows (p < 0.05), increased serum levels of surfactant protein (SP)-A (p < 0.05), SP-D (p < 0.05), Krebs von den Lungen-6 (p < 0.01), and C-reactive protein (p < 0.05) compared to those with normal levels. Furthermore, defining Δ as the value after rituximab administration minus the value before rituximab administration, baseline serum CXCL1 levels correlated with Δ percent predicted diffusing capacity for carbon monoxide (p < 0.01). In addition, ΔCXCL1 correlated with ΔSP-A (p < 0.05). Similarly, serum CXCL1 levels after rituximab administration correlated with percent predicted forced vital capacity (p < 0.05) and serum SP-D levels (p < 0.05) after rituximab. Conclusions: Our results suggest that serum CXCL1 is associated with the disease activity of SSc-ILD, and high serum CXCL1 levels are one of the predictors of improvement in SSc-ILD with rituximab.

show abstract

CXCL1: Gene, Promoter, Regulation of Expression, mRNA Stability, Regulation of Activity in the Intercellular Space

Cited by 71 publications

References 219 publications

STAT3 regulates inflammatory cytokine production downstream of TNFR1 by inducing expression of TNFAIP3/A20

STAT3 regulates inflammatory cytokine production downstream of TNFR1 by inducing expression of TNFAIP3/A20

Cytokines and chemokines multiplex analysis in patients with low disease activity rheumatoid arthritis

Serum C-X-C Chemokine Ligand 1 Levels in Patients with Systemic Sclerosis: Relationship of Clinical and Laboratory Observations to Anti-CD20 Monoclonal Antibody Administration

Contact Info

Product

Resources

About