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Expression of TLR4 gene is downregulated in acquired immune deficiency syndrome-associated Kaposi's sarcoma
Xiaobo Lu1, Xuefeng Wan2, Xiaoran Li1
1Department of Infectious Diseases, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
Abstract:
The present study investigated the expression of Toll-like receptor 4 (TLR4) and proteins involved in its associated signaling pathways in patients with classic Kaposi's sarcoma (KS) and acquired immune deficiency syndrome (AIDS)-associated KS (AIDS-KS) in Xinjiang Autonomous Region of China. A total of 35 patients with KS were enrolled in the present study between May 2011 and July 2013, including 26 cases of AIDS-KS and 9 cases of classic KS. Another 10 healthy subjects of the Uygur ethnic group were included in the normal control group. KS tissues were subjected to hematoxylin and eosin staining and immunohistochemical staining. To measure the expression of mRNA, reverse-transcription quantitative polymerase chain reaction was performed. To determine protein expression, western blot analysis was employed. AIDS-KS was mainly distributed in the face and limbs, while classic KS was mainly distributed in the limbs. The histopathological characteristics of AIDS-KS and classic KS tissues were different from those of normal tissues. TLR4 was mainly distributed in the dermis of KS tissues. The mRNA expression levels of TLR4 were reduced in classic KS and AIDS-KS. The protein expression levels of RAS, RAF, nuclear factor (NF)-κB P65 and P50 as well as inhibitor of NF-κB-α of the TLR4 signaling pathway in AIDS-KS and KS tissues were higher than those in normal tissues. In conclusion, the expression of TLR4 gene in KS tissues was decreased, while the expression of proteins of the TLR4 signaling pathway was upregulated in KS. Downregulation of TLR4 may be associated with the occurrence and development of AIDS-KS, while its restoration may represent a novel therapeutic approach for AIDS-KS.
Insights
Toll-like receptor 4 (TLR4) gene expression decreased in Kaposi's sarcoma (KS) and AIDS-KS. However, its signaling pathway proteins were upregulated, suggesting TLR4 downregulation may drive AIDS-KS development and restoration could be a therapeutic target.
Area of Science:
- Immunology
- Oncology
- Dermatology
Background:
- Kaposi's sarcoma (KS), particularly AIDS-associated KS (AIDS-KS), remains a significant health concern.
- The role of Toll-like receptor 4 (TLR4) and its signaling pathway in KS pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the expression of TLR4 and its signaling pathway proteins in classic KS and AIDS-KS.
- To explore the potential association of TLR4 with the development of AIDS-KS.
Main Methods:
- Analysis of KS tissues from 35 patients (26 AIDS-KS, 9 classic KS) and 10 healthy controls.
- Histopathological examination using hematoxylin and eosin staining.
- Immunohistochemical staining for protein localization.
- Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) for mRNA expression.
- Western blot analysis for protein expression.
Main Results:
- TLR4 mRNA expression was reduced in both classic KS and AIDS-KS tissues compared to controls.
- Protein expression of RAS, RAF, nuclear factor (NF)-κB P65 and P50, and inhibitor of NF-κB-α was elevated in KS tissues.
- TLR4 was primarily localized in the dermis of KS tissues.
Conclusions:
- Downregulation of the TLR4 gene is observed in KS tissues.
- Upregulation of TLR4 signaling pathway proteins suggests their involvement in KS pathogenesis.
- TLR4 downregulation may contribute to AIDS-KS development, and its restoration could offer a novel therapeutic strategy.