Therapeutic effects of lactosyl derivative Gu-4 in a collagen-induced arthritis rat model.
Rheumatoid arthritis (RA) is an inflammatory disorder that is characterized by persistent recurrence of joint inflammation leading to cartilage and bone destruction. The present anti-arthritis therapies failed to achieve satisfactory remission in all patients; therefore, it is still necessary to develop novel approaches to fulfill the demand in clinic. Here, we reported the therapeutic effects of lactosyl derivative Gu-4, a synthetic compound that was previously identified as a selective inhibitor against leukocyte integrin CD11b, in a bovine type II collagen induced arthritis (CIA) rat model. First, prophylactic administration of Gu-4 (1.2728 mg/kg) to rats by intraperitoneal injection every 2 days from the first day of collagen immunization significantly decreased the incidence of CIA, diminished the mean paw volume increase, and reduced the number of swollen paws. Second, administration of Gu-4 (1.2728 mg/kg) to rats at early-onset stage of CIA prevented the progression of the pathological process of RA, accelerated the remission of paw edema, and declined the arthritis score; after 5 weeks treatment, X-ray and histological examinations were carried out, the ankle joint of hind limb of Gu-4 treated CIA rats exhibited slighter bone erosion and much less inflammatory cell infiltration compared to those of saline treated animals; furthermore, Gu-4 remarkably attenuated the production of rheumatoid factor (RF) in the serum of CIA rats as determined by ELISA. Moreover, we performed in vitro lymphocyte proliferation assay and found that Gu-4 significantly inhibited the proliferation of splenic lymphocytes isolated from CIA rats in a dose-dependent manner. Our results suggest that Gu-4 can effectively ameliorate CIA and might be an alternative option for the treatment of RA.
Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China.
Jie
J
Fan
Huiting
H
Zhou
Shihui
S
Wang
Hailian
H
Wang
Yushun
Y
Zhang
Yingtao
Y
Guo
Qing
Q
Li
Zhongjun
Z
Li
Zhihui
Z
Zhao
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024043:Collagen Type II; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004487:Edema / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000068800:Etanercept; D005260:Female; D005973:Glutamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology / Q000627:therapeutic use; D007596:Joints / Q000187:drug effects* / Q000473:pathology; D007785:Lactose / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012217:Rheumatoid Factor / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D024043:Collagen Type II; C540504:Gu-4 compound; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D005973:Glutamine; D012217:Rheumatoid Factor; D007785:Lactose; D000068800:Etanercept