title: Early pregnancy factor treatment suppresses the inflammatory response and adhesion molecule expression in the spinal cord of SJL/J mice with experimental autoimmune encephalomyelitis and the delayed-type hypersensitivity reaction to trinitrochlorobenzene in normal BALB/c mice.
abstract: Early pregnancy factor (EPF) is a secreted protein, present in serum during early pregnancy and essential for maintaining viability of the embryo. It is a homologue of chaperonin 10 (Cpn10) but, unlike Cpn10, it has an extracellular role. EPF has immunosuppressive and growth regulatory properties. Previously we have reported the preparation of recombinant EPF (rEPF) and shown that treatment with rEPF will suppress clinical signs of MBP-EAE in Lewis rats and PLP-EAE in SJL/J mice. In the present study, these findings have been extended to investigate possible mechanisms involved in the action of EPF. Following treatment of mice with rEPF from the day of inoculation, there were fewer infiltrating CD3+ and CD4+ cells in the parenchyma of the spinal cord during the onset of disease and after the initial episode, compared with mice treated with vehicle. Expression of the integrins LFA-1, VLA-4 and Mac-1 and of members of the immunoglobulin superfamily of adhesion molecules ICAM-1 and VCAM-1 was suppressed in the central nervous system (CNS) following rEPF treatment. The expression of PECAM-1 was not affected. To determine if rEPF suppressed T cell activation in the periphery, the delayed-type hypersensitivity (DTH) reaction of normal BALB/c mice to trinitrochlorobenzene (TNCB) following treatment with rEPF was studied. The results showed that treatment with rEPF suppressed the DTH reaction, demonstrating the ability of EPF to downregulate the cell-mediated immune response. These results indicate that suppression of immunological mechanisms by rEPF plays a major role in the reduction of clinical signs of disease in experimental autoimmune encephalomyelitis (EAE).
authors.affiliation: Department of Surgery, The University of Queensland, Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Michael D
authors.initials: MD
authors.lastname: Walsh
authors.forename: Kim B
authors.initials: KB
authors.lastname: Nguyen
authors.forename: Narelle C
authors.initials: NC
authors.lastname: Hillyard
authors.forename: Alice C
authors.initials: AC
authors.lastname: Cavanagh
authors.forename: Pamela A
authors.initials: PA
authors.lastname: McCombe
authors.forename: Halle
authors.initials: H
authors.lastname: Morton
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018835:Chaperonin 10; D044842:Cullin Proteins; D003711:Demyelinating Diseases; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000188:drug therapy*; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy; D039041:Integrin alpha4beta1 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D010853:Picryl Chloride / Q000494:pharmacology; D011247:Pregnancy; D011257:Pregnancy Proteins; D017483:Receptors, Vasopressin / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013491:Suppressor Factors, Immunologic; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D018835:Chaperonin 10; C094547:Cul5 protein, rat; D044842:Cullin Proteins; D039041:Integrin alpha4beta1; D008565:Membrane Proteins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D010455:Peptides; D011257:Pregnancy Proteins; D017483:Receptors, Vasopressin; D011994:Recombinant Proteins; D013491:Suppressor Factors, Immunologic; C025124:early pregnancy factor; C435023:myelin proteolipid protein (139-151); D010853:Picryl Chloride