Expression of TNF-alpha and related signaling molecules in the peripheral blood mononuclear cells of rheumatoid arthritis patients.
We examined the role of tumor necrosis factor (TNF-alpha) and its related signaling intermediates leading to apoptosis/proliferation in the peripheral blood mononuclear cells (PBMCs) of RA patients. The constitutive expression of mRNA for TNF-alpha receptors (TNFR-I and TNFR-II) and the adapter molecules, such as the TNF receptor-associated death domain protein (TRADD), Fas-associated death domain protein (FADD), receptor interacting protein (RIP), and TNF receptor-associated factor 2 (TRAF-2) were analyzed by reverse transcriptase-PCR (RT-PCR) in PBMCs from control and RA cases. PBMCs of RA patients showed a significant increase in TNF-alpha and TNFR-I expression as compared with that from control subjects along with significantly increased constitutive expression of TRADD, RIP, and TRAF-2 mRNA. There was a decrease in expression of FADD in RA patients, but the difference was not significant as compared to controls. These data suggested enhanced signaling by the TNFR-I-TRADD-RIP-TRAF-2 pathway and suppressed signaling by the TNFR-I-TRADD-FADD pathway in PBMCs of RA patients. However, the regulatory mechanisms for TNF-alpha induced signaling may not be explained only by these pathways.
Raghav
Sunil Kumar
SK
Institute of Genomics and Integrative Biology, Delhi University Campus, Mall Road, Delhi 110 007, India.
Gupta
Bhawna
B
Agrawal
Charu
C
Chaturvedi
Ved P
VP
Das
Hasi R
HR
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000502:physiology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D047992:TNF Receptor-Associated Factor 2; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases