A Broad Blockade of Signaling from the IL-20 Family of Cytokines Potently Attenuates Collagen-Induced Arthritis.

Two heterodimeric receptors consisting of either IL-20R1 or IL-22R1 in complex with a common ß receptor subunit IL-20R2 are shared by three of the IL-20 family of cytokines: IL-19, IL-20, and IL-24. These proinflammatory cytokines have been implicated in the pathogenesis of some autoimmune diseases, including rheumatoid arthritis (RA), psoriasis, and atopic dermatitis. Although mAbs against IL-19 and IL-20 have each been shown to modulate disease severity of collagen-induced arthritis in animal models, and anti-IL-20 therapeutic Ab has exhibited some efficacy in the treatment of RA in clinical trials, benefits for a complete blockade of these functionally redundant cytokines remain to be explored. In this report, we show that recombinant human soluble IL-20R2-Fc fusion protein binds to IL-19, IL-20, and IL-24 with similar high affinity and blocks their signaling in vitro. In DBA/1 mouse collagen-induced arthritis model, recombinant human IL-20R2-Fc exhibits comparable efficacy as TNF blocker etanercept in the treatment of established arthritis, whereas the combined use of both biologics manifests little synergistic therapeutic effects. In situ ligand-receptor functional binding analysis shows that a large amount of immune infiltrates expressing high levels of TNFR and IL-20 subfamily cytokines congregate within the inflamed disease tissues. Colocalization experiments reveal that signals from IL-20R2 and TNF transduction pathways seem to converge in macrophages and function in tandem in orchestrating the pathogenesis of RA. Elucidation of this interaction provides a better understanding of cytokine cross-talk in RA and a rationale for more effective biologic therapies that target IL-20R2 instead of individual cytokines from IL-20 family.

[Affinity Detection and Quantification of Receptors of TRAIL Based on Their Thermostability].

OBJECTIVE: To develop a way for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors quantification in cancer via its' thermostability. METHODS: Endougenous alkaline phosphatase (AP) activity and denaturation temperature of pancreatic cancer cell lines AsPC-1 and Capan-2 were detected. Boiling treated recombinant protein death receptor 5 (DR5), named DR5 AP, as well as pancreatic cancer cells lines AsPC-1 and Capan-2 were incubated with AP-tagged TRAIL (AP-TRAIL), and then reacted with Reagent A and Reagent S, the substrate of AP, to quantitive and in site detection of the receptor. RESULTS: The endougenous AP activity of pancreatic cancer cells lines AsPC-1 and Capan-2 could not be totally inactivated by incubated at 65 °C, thus inhibited the detection of TRAIL receptor, but the activity was dramatically decreased after treated with boiling water, whereas the DR5-AP was thermal stable. The surface receptor of AsPC-1 and Capan-2 could be recognized and bound by AP-TRAIL after treated at 100 °C, the readings were 2. 210±0. 393 and 2. 027±0. 019. CONCLUSION: The TRAIL receptors are thermostable and this may provide a better diagnosis and prognosis of cancer as well as personalize cancer therapy.