Regulation of chemokines and chemokine receptors after experimental closed head injury.
The expression of the chemokines macrophage inflammatory protein (MIP)-2 and MIP-1alpha and of their receptors CXCR2 and CCR5 was assessed in wild type (WT) and TNF/lymphotoxin-alpha knockout (TNF/LT-alpha-/-) mice subjected to closed head injury (CHI). At 4 h after trauma intracerebral MIP-2 and MIP-1alpha levels were increased in both groups with MIP-2 concentrations being significantly higher in WT than in TNF/LT-alpha-/- animals (p < 0.05). Thereafter, MIP-2 production declined rapidly, whereas MIP-1alpha remained elevated for 7 days. Expression of CXCR2 was confined to astrocytes and increased dramatically within 24 h in both mouse types. Contrarily, CCR5 expression remained constitutively low and was mainly localized to microglia. These results show that after CHI, chemokines and their receptors are regulated differentially and with independent kinetics.
Otto
V I
VI
Divisions of Research and Trauma Surgery, Department of Surgery, University Hospital, CH-8091 Zurich, Switzerland.
Stahel
P F
PF
Rancan
M
M
Kariya
K
K
Shohami
E
E
Yatsiv
I
I
Eugster
H P
HP
Kossmann
T
T
Trentz
O
O
Morganti-Kossmann
M C
MC
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism*; D004660:Encephalitis / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000502:physiology; D016489:Head Injuries, Closed / Q000378:metabolism* / Q000503:physiopathology; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D015846:Monokines / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines; D008233:Lymphotoxin-alpha; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D023063:Receptors, Interleukin-8B; D014409:Tumor Necrosis Factor-alpha