Differential regulation of the CXCR2 chemokine network in rat brain trauma: implications for neuroimmune interactions and neuronal survival.
Chemokine receptors represent promising targets to attenuate inflammatory responses and subsequent secondary damage after brain injury. We studied the response of the chemokines CXCL1/CINC-1 and CXCL2/MIP-2 and their receptors CXCR1 and CXCR2 after controlled cortical impact injury in adult rats. Rapid upregulation of CXCL1/CINC-1 and CXCL2/MIP-2, followed by CXCR2 (but not CXCR1), was observed after injury. Constitutive neuronal CXCR2 immunoreactivity was detected in several brain areas, which rapidly but transiently downregulated upon trauma. A second CXCR2-positive compartment, mainly colocalized with the activated microglia/macrophage marker ED1, was detected rapidly after injury in the ipsilateral cortex, progressively emerging into deeper areas of the brain later in time. It is proposed that CXCR2 has a dual role after brain injury: (i) homologous neuronal CXCR2 downregulation would render neurons more vulnerable to injury, whereas (ii) chemotaxis and subsequent differentiation of blood-borne cells into a microglial-like phenotype would be promoted by the same receptor.
Solvay Pharmaceuticals Research Laboratories, C. J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands.
Astrid
A
Vallès
Lindsay
L
Grijpink-Ongering
Freddy M
FM
de Bree
Tinka
T
Tuinstra
Eric
E
Ronken
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001925:Brain Damage, Chronic / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications*; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000276:immunology*; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology; D053331:Ectodysplasins; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D005911:Gliosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D017628:Microglia / Q000276:immunology; D009410:Nerve Degeneration / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D015213:Neuroimmunomodulation / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D023063:Receptors, Interleukin-8B / Q000276:immunology* / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D015415:Biomarkers; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; C513296:Cxcl2 protein, rat; D053331:Ectodysplasins; D008565:Membrane Proteins; D023063:Receptors, Interleukin-8B; D048069:Tumor Necrosis Factors