Progesterone administration modulates TLRs/NF-kappaB signaling pathway in rat brain after cortical contusion.
This study investigated whether progesterone administration modulates toll-like receptors (TLRs) and the nuclear factor-kappa B (NF-kappaB) signaling pathway in the injured rat brain following traumatic brain injury (TBI). Right parietal cortical contusion was made by a weight-dropping method. Male rats were given 0 or 16 mg/kg injections of progesterone at postinjury hr 1 and 6 and on days 1, 2, 3, 4, and 5. Brain samples were extracted at 5 days after trauma. We measured mRNA expression of TLR2 and TLR4 by reverse-transcriptase polymerase chain reaction (RT-PCR), NF-kappaB binding activity by electrophoretic mobility shift assay (EMSA), concentrations of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA), intercellular adhesion molecule-1 (ICAM-1) expression by immunohistochemistry, and brain damage by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). The results showed that TBI induces strong up-regulation of TLR2, TLR4, NF-kappaB, pro-inflammatory cytokines, and ICAM-1 in the pericontusional area. Administration of progesterone following TBI down-regulates the cortical levels of these agents related to the TLRs/NF-kappaB signaling pathway. After progesterone administration, apoptotic TUNEL-positive cells in the injured brain were significantly decreased. In summary, post-TBI progesterone administration attenuates the TLRs/NF-kappaB signaling pathway in injured rat brain, and this may be a mechanism whereby progesterone improves the outcome following TBI.
Chen
Gang
G
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, PR China.
Shi
Jixin
J
Jin
Wei
W
Wang
Lin
L
Xie
Weiying
W
Sun
Jie
J
Hang
Chunhua
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011374:Progesterone / Q000008:administration & dosage* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D011374:Progesterone