Knockdown of Fcγ receptor III in an arthritic temporomandibular joint reduces the nociceptive response in rats.
Knockdown of Fcγ receptor III in an arthritic temporomandibular joint reduces the nociceptive response in rats.
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DOI：
10.1002/art.27630
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发表时间：
2010-10
影响因子：
--
通讯作者：
Bellinger, Larry L.
中科院分区：
文献类型：
--
作者：
Kramer, Phillip R.;Puri, Jyoti;Bellinger, Larry L.
FcγRIII（CD 16）是免疫细胞上表达的一种受体，可选择性结合免疫球蛋白G（IgG）分子，IgG结合导致细胞活化和细胞因子释放。IgG是关节炎中的重要因素，并且可以在关节炎性颞下颌关节（TMJ）中发现。我们假设TMJ组织中FcγRIII表达的减少将减少炎症关节中的伤害性和炎症反应。为了检验这一假设，将裸的或与线性聚乙烯亚胺（PEI）复合的siRNA注射到TMJ的上级关节间隙中。在施用siRNA后，用盐水或完全弗氏佐剂（CFA）注射关节以诱导关节炎。通过测量动物的进食持续时间来定量大鼠的伤害性反应。用免疫细胞化学或western方法检测TMJ组织中FcγRIII的表达。用5′ RACE法检测FcγRIII转录本的切割情况。ELISA法测定TMJ组织中IL-1 β和IgG含量。结果表明，注射FcγRIII siRNA减少了TMJ组织中FcγRIII的量，并且转录物以与RNA干扰机制一致的方式被切割。此外，注射FcγRIII siRNA降低了关节炎TMJ大鼠的伤害性反应，并减少了促炎细胞因子IL-1β的量。我们得出结论，FcγRIII有助于TMJ炎性关节炎引起的疼痛，siRNA有可能成为这种疾病的有效治疗方法。
FcγRIII (CD16) is a receptor expressed on immune cells that selectively binds immmunoglobulin G (IgG) molecules, IgG binding results in cellular activation and cytokine release. IgG is an important factor in arthritis and can be found in arthritic temporomandibular joints (TMJ). We hypothesize that a reduction in FcγRIII expression in the TMJ tissues will reduce the nociceptive and inflammatory response in an inflamed joint. To test this hypothesis siRNA, either naked or complexed with linear polyethylenimine (PEI) was injected into the superior joint space of the TMJ. After administration of siRNA the joint was injected with saline or with complete Freund’s adjuvant (CFA) 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. Cleavage of FcγRIII transcript was then assayed by 5′ rapid amplification of cDNA ends method (5′ RACE). Interleukin-1β (IL-1β) and IgG content was measured in the TMJ tissue by ELISA. The results indicate that injection of FcγRIII siRNA reduced the amount of FcγRIII in the TMJ tissues and that the transcript was cleaved in a manner consistent with a RNA interference mechanism. Moreover, injection of FcγRIII siRNA reduced the nociceptive response of rats with an arthritic TMJ and reduced the amount of pro-inflammatory cytokine IL-1β. We conclude that FcγRIII contributes to the pain resulting from inflammatory arthritis of the TMJ and that siRNA has the potential to be an effective treatment for this disorder.
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影响因子：
3.6
作者：
Kerins, CA;Carlson, DS;Bellinger, LL
通讯作者：
Bellinger, LL
影响因子：
3
作者：
Hutchins, B;Spears, R;Harper, RP
通讯作者：
Harper, RP
影响因子：
--
作者：
Kramer, PR;Kramer, SF;Guan, G
通讯作者：
Guan, G
影响因子：
46.9
作者：
Jackson, AL;Bartz, SR;Linsley, PS
通讯作者：
Linsley, PS
影响因子：
46.9
作者：
Judge, AD;Sood, V;MacLachlan, I
通讯作者：
MacLachlan, I