OBJECTIVE: Fcγ receptor III (FcγRIII; CD16) is a receptor expressed on immune cells that selectively binds IgG molecules. IgG binding results in cellular activation and cytokine release. IgG is an important factor in arthritis and can be found in the arthritic temporomandibular joint (TMJ). We undertook this study to test the hypothesis that a reduction in FcγRIII expression in TMJ tissues would reduce the nociceptive and inflammatory responses in an inflamed joint. METHODS: Small interfering RNA (siRNA), either naked or complexed with linear polyethyleneimine, was injected into the superior joint space of the TMJ in rats. After administration of siRNA the joint was injected with saline or with Freund's complete adjuvant to induce arthritis. Nociceptive responses were quantitated in the rat by measuring the animal's meal duration. FcγRIII expression in the TMJ tissue was assayed by immunocytochemistry or Western blotting. Cleavage of FcγRIII transcript was then assayed by 5' rapid amplification of complementary DNA ends. Interleukin-1β (IL-1β) and IgG content was measured in the TMJ tissue by enzyme-linked immunosorbent assay. RESULTS: Injection of FcγRIII siRNA reduced the amount of FcγRIII in the TMJ tissues, and the transcript was cleaved in a manner consistent with an RNA interference mechanism. Moreover, injection of FcγRIII siRNA reduced the nociceptive response of rats with an arthritic TMJ and reduced the amount of the proinflammatory cytokine IL-1β. CONCLUSION: FcγRIII contributes to the pain resulting from inflammatory arthritis of the TMJ, and siRNA has the potential to be an effective treatment for this disorder.
OBJECTIVE: Fcγ receptor III (FcγRIII; CD16) is a receptor expressed on immune cells that selectively binds IgG molecules. IgG binding results in cellular activation and cytokine release. IgG is an important factor in arthritis and can be found in the arthritic temporomandibular joint (TMJ). We undertook this study to test the hypothesis that a reduction in FcγRIII expression in TMJ tissues would reduce the nociceptive and inflammatory responses in an inflamed joint. METHODS: Small interfering RNA (siRNA), either naked or complexed with linear polyethyleneimine, was injected into the superior joint space of the TMJ in rats. After administration of siRNA the joint was injected with saline or with Freund's complete adjuvant to induce arthritis. Nociceptive responses were quantitated in the rat by measuring the animal's meal duration. FcγRIII expression in the TMJ tissue was assayed by immunocytochemistry or Western blotting. Cleavage of FcγRIII transcript was then assayed by 5' rapid amplification of complementary DNA ends. Interleukin-1β (IL-1β) and IgG content was measured in the TMJ tissue by enzyme-linked immunosorbent assay. RESULTS: Injection of FcγRIII siRNA reduced the amount of FcγRIII in the TMJ tissues, and the transcript was cleaved in a manner consistent with an RNA interference mechanism. Moreover, injection of FcγRIII siRNA reduced the nociceptive response of rats with an arthritic TMJ and reduced the amount of the proinflammatory cytokine IL-1β. CONCLUSION: FcγRIII contributes to the pain resulting from inflammatory arthritis of the TMJ, and siRNA has the potential to be an effective treatment for this disorder.
Authors: Peter C Scacheri; Orit Rozenblatt-Rosen; Natasha J Caplen; Tyra G Wolfsberg; Lowell Umayam; Jeffrey C Lee; Christina M Hughes; Kalai Selvi Shanmugam; Arindam Bhattacharjee; Matthew Meyerson; Francis S Collins Journal: Proc Natl Acad Sci U S A Date: 2004-02-09 Impact factor: 11.205
Authors: Yukihide Tomari; Tingting Du; Benjamin Haley; Dianne S Schwarz; Ryan Bennett; Heather A Cook; Birgit S Koppetsch; William E Theurkauf; Phillip D Zamore Journal: Cell Date: 2004-03-19 Impact factor: 41.582
Authors: Paschalia M Mountziaris; David C Sing; Sue Anne Chew; Stephanie N Tzouanas; E Dennis Lehman; F Kurtis Kasper; Antonios G Mikos Journal: Pharm Res Date: 2010-12-24 Impact factor: 4.200
Authors: Paschalia M Mountziaris; Stephanie N Tzouanas; David C Sing; Phillip R Kramer; F Kurtis Kasper; Antonios G Mikos Journal: Acta Biomater Date: 2012-06-28 Impact factor: 8.947