Cyclo-oxygenases and prostaglandins in acute inflammatory demyelination of the peripheral nerve.
OBJECTIVE
To investigate the expression of cyclo-oxygenases (COX), key enzymes in propagating inflammatory responses by converting arachidonic acid to prostaglandins, in inflammatory demyelinating disorders of the peripheral nervous system (PNS).


METHODS
Expression and distribution of COX messenger RNA (mRNA) and protein were studied in sural nerve biopsies, serum, and CSF samples from patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), or, for comparison, with vasculitic neuropathy (VN), which is a inflammatory nondemyelinating disorder, and noninflammatory neuropathies (NIN) using RT-PCR, immunohistochemistry, and immunoblotting. To confirm functional COX-2 activity, the expression of prostaglandin E(2) (PGE(2)) and prostaglandin F(2alpha) (PGF(2alpha)) was evaluated by ELISA ex vivo and in vitro.


RESULTS
Whereas COX-1 expression was unaltered in all investigated groups, a significant upregulation of COX-2 mRNA was detected in sural nerves from patients with GBS, CIDP, or VN but not in control subjects with noninflammatory disorders. Macrophages were identified as its primary cellular source. Increased COX-2 protein levels were detectable in serum and CSF from all patients with GBS and, in smaller numbers only, in samples from patients with CIDP or VN but not from the NIN group studied. Moreover, increased levels of PGE(2) and PGF(2alpha) were measurable in sera from patients with GBS, CIDP, or VN and in cell culture supernatants from in vitro stimulated macrophages, indicative of COX-2 activity.


CONCLUSIONS
Cyclo-oxygenase-2, expressed by macrophages, may generate prostaglandins during acute inflammatory demyelination of the peripheral nerve.
Hu
Wei
W
Department of Neurology, Research Group for Clinical and Experimental Neuroimmunology, Heinrich-Heine University, Düsseldorf, Germany.
Mathey
Emily
E
Hartung
Hans-Peter
HP
Kieseier
Bernd C
BC
D000208:Acute Disease; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D003711:Demyelinating Diseases / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D020275:Guillain-Barre Syndrome / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007527:Isoenzymes / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology; D008565:Membrane Proteins; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000378:metabolism / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood / Q000134:cerebrospinal fluid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013497:Sural Nerve / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D014657:Vasculitis / Q000150:complications
D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D012333:RNA, Messenger; D015237:Dinoprost; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone