Disease relevance of Cxcl2

• In the present report, we describe recombinant production of CINC-2 alpha, CINC-2 beta and CINC-3 in Escherichia coli, and biological properties of these chemokines [1].
• These data suggest a role for the nitric oxide pathway in the overproduction of pro-inflammatory mediators IL-6 and MIP-2 during GBS-induced lung inflammation [2].
• These results indicate that CINCs, especially CINC-1 and CINC-3 play an important role in the recruitment of neutrophils to the lung in LPS-induced acute lung injury [3].
• GRO chemokine mRNAs were rapidly expressed in inflamed glomeruli during immune complex glomerulonephritis with MIP-2 predominating over CINC [4].
• The purpose of the present study was to investigate whether Chlamydophila pneumoniae (I) alters the expression of TLR2 and/orTLR4 in type II cells in a (II) Rho-GTPase- and (III) NF-kappaB-dependent pathway, subsequently (IV) leading to the production of (IV) pro-inflammatory TNF-alpha and MIP-2 [5].

High impact information on Cxcl2

• These findings were associated with a reduction in eotaxin mRNA and an increase in mRNA for the T-cell chemokines macrophage inflammatory protein-2 (MIP-2), MIP-1beta, and RANTES [6].
• Lung lavage levels of TNFalpha, IL-1beta, IL-6, IL-10, MIP-2, and IFNgamma were measured by ELISA [7].
• The expression of MIP-2 correlated with glomerular neutrophil influx [8].
• The role of the chemokine, macrophage inflammatory protein-2 (MIP-2), during anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was studied [8].
• Modulation of neutrophil influx in glomerulonephritis in the rat with anti-macrophage inflammatory protein-2 (MIP-2) antibody [8].

Chemical compound and disease context of Cxcl2

• Nitric oxide induces MIP-2 transcription in rat renal mesangial cells and in a rat model of glomerulonephritis [9].
• Since chemokines, secreted by activated glial cells, play a prominent role in eliciting inflammatory responses in the central nervous system, the effects of Tau-Cl on production of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) were determined in activated C6 glioma cells [10].
• Administration of estradiol or the testosterone receptor antagonist, flutamide, to male rats abrogated the increase in gut injury and the increased IL-6 and MIP-2 response observed after hypoxia plus acidosis [11].
• METHODS: Macrophage inflammatory protein-2 (MIP-2), a rat ELR+ CXC chemokine, or live Klebsiella pneumoniae (K. pneumoniae) was administered it to induce alveolar neutrophil migration in the absence or presence of acute ethanol intoxication [12].
• Recently, CINCs were grouped into four subtypes-CINC-1, CINC-2alpha, CINC-2beta, and CINC-3-and CINC-1 was considered to be a major isoform among the four CINCs in LPS-induced acute lung inflammation in rats [13].

Biological context of Cxcl2

• The complete amino acid sequences of purified CINC-2 alpha and CINC-3 were determined by analysis of the fragments isolated from proteinase V8-treated CINCs [14].
• Both cell phenotypes secreted MIP-2 and MCP-1 in response to IL-1beta or lipopolysaccharide, but there was no priming or synergy with ozone [15].
• Kinetics of the neutrophil (MIP-2) and macrophage (MIP-1 alpha) chemokines revealed an early onset (12-24 h), a plateau from 1 to 4 days, and expression abruptly declining by Day 6 [16].
• Deletion and mutational analysis identified critical nuclear factor (NF)-kB and NF-IL-6 binding sites required for NO regulation of MIP-2 [9].
• We cloned 770 bp of the 5'-flanking region of rat MIP-2 and fused this fragment to a luciferase reporter gene [9].

Anatomical context of Cxcl2

• Our results show that CINC, in contrast to MIP-2, is selectively transported from the lung to the systemic circulation, where it promotes neutrophil migration into the lung in response to a chemotactic stimulus [17].
• Nitric oxide production and levels of MCP-1 and MIP-2 were increased in the 24-hr culture media of alveolar macrophages (AMs) obtained on day 1 [18].
• TNF-alpha increased the number of macrophages and MCP-1 mRNA expression in scarred mucosa from 4 h, whereas it increased MPO activities (marker of neutrophil infiltration) and mRNA expression of MIP-2 and CINC-2alpha from 24 h [19].
• MIP-1 alpha, MIP-2, and RANTES may be responsible for recruiting macrophages, granulocytes, and lymphocytes, respectively, to the rejecting allograft [16].
• In vitro, the production of CINC-1 and CINC-3 from LPS-stimulated macrophages was significantly elevated compared to unstimulated macrophages 6 h later [3].

Associations of Cxcl2 with chemical compounds

• These effects were transient as rmIL-1beta-stimulated AT II cell secretions of interleukin-6 and MIP-2 progressively reached control values between 4 and 24 h after the end of halothane exposure [20].
• Pentoxifylline inhibited the indomethacin-induced gastric injury with reduction of neutrophil infiltration and expression of chemokine (MCP-1, MIP-2, and CINC-2alpha) [19].
• Addition of L-arginine (L-arg) reversed the AG effect on IL-6 and MIP-2 expression [2].
• Further, dietary glycine largely prevented increases in IL-1beta and TNF-alpha in the colon 2 days after TNBS, and TNBS induction of CINC and MIP-2 in the colonic tissue also was abrogated by glycine [21].
• Moreover, inhibition of IL-1b-induced endogenous NO formation by the NO-synthase (NOS) inhibitor L-NMMA markedly attenuated MIP-2 protein expression [9].

Regulatory relationships of Cxcl2

• However, MCP-1 inhibition persisted until 24 h. rmIL-1beta-induced MIP-2 and tumor necrosis factor-alpha mRNA expression were decreased by 36 and 24%, respectively, after halothane exposure [20].
• CINC-3 induced enhancement of cytoplasmic calcium concentration more potently than CINC-1 and CINC-2, and desensitized calcium transients induced by CINC-1 and CINC-2, which were essentially identical to those observed in rat neutrophils [22].
• A study was performed to determine whether IL-1 beta could induce the expression of MIP-2 in the lungs of Brown-Norway rats [23].
• Finally, IL-1beta but not IFN-gamma or IL-4 enhanced MIP-2 mRNA levels [24].
• TNF-alpha also induced MIP-2 production from alveolar epithelial cells [25].

Other interactions of Cxcl2

• On the basis of their N-terminal amino acid sequences, one of the chemokines was identical with rat GRO/cytokine-induced neutrophil chemoattractant (CINC) which we reported previously, and another was identical with rat macrophage inflammatory protein-2 (MIP-2) [14].
• Neither CINC-2 beta nor CINC-3 were detected during the entire course of the infection [26].
• MIP-1 alpha, MIP-2, and RANTES were expressed only in allografts [16].
• In situ hybridisation of lungs using MIP-2 cDNA probe labelled with digoxigenin showed expression of MIP-2 mRNA in airway mononuclear cells and airway epithelium at four hours after IL-1 beta; at 24 hours the signal had nearly gone [23].
• In summary, we have shown that TII alveolar epithelial cells produce three of the major proinflammatory CXC chemokines (GRO, CINC-2alpha, and MIP-2) and their cognate receptor CXCR2 [27].

Analytical, diagnostic and therapeutic context of Cxcl2

• Finally, by in situ hybridization techniques, PMN in the lung tissue, particularly those located in the vicinity of the bronchiole and vasculature, were demonstrated to localize MIP-2 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)[28]
• Instillation of recombinant MIP-2 or CINC into the lung increased the number of neutrophils recovered in bronchoalveolar lavage fluid at 4 h, and this effect was enhanced when both chemokines were administered together [17].
• MIP-2 transcription increased on PAD 12, while in autografts, its expression was not markedly different from that detected in the contralateral, non-grafted peripheral cornea [29].
• The biotin-streptavidin sandwich ELISA for CINC-2 beta detected CINC-2 alpha and CINC- 2 beta equally well between 1 ug/mI and 300 ng/ml, but did not show cross-reactivity with CINC-1 and CINC-3 [30].
• The levels of CINC-1, CINC-2alpha and CINC-3 in BAL fluids were significantly higher in the LPS group than in the saline-instilled control group [3].

References