Placental immunomodulator ferritin, a novel immunoregulator, suppresses experimental arthritis

Abstract

Objective. To determine the effect of treatment with C48, the recombinant cytokine-like domain of the novel human placental immunomodulator ferritin (PLIF) immunoregulator, on zymosan-induced arthritis (ZIA) in mice and on adjuvant-induced arthritis (AIA) in rats.Methods. The in vitro effect of PLIF/C48 was tested in mixed lymphocyte cultures (MLCs) of allogeneic mouse splenocytes. Arthritis was induced by intraarticular injection of zymosan into naive mice and by subcutaneous injection of Mycobacterium tuberculosis into rats. C48 was injected intraperitoneally daily from day 3 to day 9 or from day 7 to day 13 after induction of synovitis by zymosan, and every other day from day 2 to day 14 after induction of AIA. Swelling of the joints and histologic features of the synovium were assessed. Th1 and Th2 cytokines were quantified by enzyme-linked immunosorbent assay.Results. Both PLIF and C48 significantly inhibited the in vitro immunoreactivity of mouse splenocytes in MLCs. Treatment of ZIA mice and AIA rats with C48 effectively reduced joint swelling. C48 treatment reduced synovial lining thickening, numbers of mononuclear cells and histiocytes, as well as cartilage destruction and bone erosions. In vitro, activated splenocytes from C48-treated ZIA and AIA animals produced significantly higher levels of interleukin-10 (IL-10). In animals with ZIA, this was accompanied by lower levels of tumor necrosis factor and IL-2.Conclusion. Human PLIF and C48 were shown to exert cross-species immunosuppressive activity in vitro. The in vivo suppression of articular inflammation in the experimental models of ZIA and AIA was the result of treatment with the antiinflammatory human C48. These results suggest that treatment with C48 may offer an effective immunotherapeutic means of controlling inflammatory polyarthritis.Several reports have described the high frequency of remission of rheumatoid arthritis (RA) during pregnancy (1-7). Similarly, most studies of pregnancy in patients with multiple sclerosis showed tendencies toward remissions during gestation and relapses during the postpartum period. Indeed, most pregnant women with RA have reported improvement of joint pain and/or swelling. A postpartum flare, however, can occur in the majority of women up to 8 weeks after delivery (7). Therefore, the state of pregnancy serves as a powerful and natural research means of identifying potential pathophysiologic mechanisms that modify disease activity and of generating innovative strategies for the development of new therapies for use in the nonpregnant state.The phenomenon of remission in RA can be attributed to several factors, one of which, an increase in estrogen secretion, occurs in pregnancy (8-10). In a collagen-induced arthritis animal model, administration of estrogen in the postpartum period prevented the postpartum flare (9). Another possible explanation for the decrease in arthritis during pregnancy and the postpartum flare of RA is the finding that glycosylation of IgG decreases during pregnancy and increases during the...

Attenuation of pain and inflammation in adjuvant‐induced arthritis by the proteasome inhibitor MG132

“…The numbers of p50‐positive cells in the cartilage and in the bone were manually counted. The synovium was graded according to the percentage of positive cells, as described previously (26), by two observers (ASA and LH) who were blinded to the treatment group. The immunoreactivity was measured as the area (in mm 2 ), using Easy Analysis software (Bergström Instruments), as previously described (29).…”

Microarray analysis of differential utilization of plant-based diets by rainbow trout

“…The expression of FTH1 is known to affect iron homeostasis, cell proliferation and lipid peroxidation (Goralska et al 1998;McLeish et al 1980;Cozzi et al 1990). FTH1 has also been shown to play a role in inhibiting apoptosis and immune function (Seldon et al 2003;Weinberger et al 2003). The other upregulated genes, SKAP2 and SDHB are linked to metabolic, immune function, cell growth and oxidative stress.…”

Silencing the expression of connexin 43 decreases inflammation and joint destruction in experimental arthritis

“…The sections were stained with hematoxylin and eosin (H&E), or safranin O. Arthritic changes, such as infiltration of inflammatory cells, synovial proliferation, destruction of articular cartilage, and bone erosion, were evaluated histologically as described. 17 To investigate the activity of osteoclastic bone resorption in vivo, sections were stained with a tartrate-resistant acid phosphate (TRAP) staining kit (Hokudo, Sapporo, Japan). 18 To investigate the effects of siCx43 on other tissues, the heart, kidneys, and testes of each rat were excised as described above, and sections of each were stained with H&E.…”