Tumor necrosis factor alpha and adalimumab differentially regulate CD36 expression in human monocytes

Area of Science:

• Immunology
• Cardiovascular Biology
• Molecular Biology

Background:

• Chronic inflammatory diseases increase cardiovascular risk.
• Tumor necrosis factor alpha (TNFalpha) plays a role in inflammation and atherosclerosis.
• CD36 expression on monocytes influences the uptake of oxidized low-density lipoproteins (LDLs) and atherosclerosis development.

Purpose of the Study:

• To investigate the role of TNFalpha and adalimumab in regulating CD36 expression in human monocytes.
• To elucidate the molecular mechanisms, including PPARgamma and redox signaling, involved in CD36 regulation by TNFalpha and adalimumab.

Main Methods:

• Human monocytes were isolated from healthy donors.
• CD36 expression was assessed using RT-PCR and flow cytometry.
• Involvement of PPARgamma, redox signaling (NADPH oxidase), and adalimumab's Fc fragment was investigated using specific inhibitors and assays.

Main Results:

• TNFalpha significantly inhibited both membrane and mRNA expression of CD36, mediated by reduced PPARgamma activation.
• Adalimumab significantly increased both membrane and mRNA expression of CD36.
• Adalimumab's induction of CD36 was independent of its Fc portion and involved activation of NADPH oxidase and redox signaling.

Conclusions:

• TNFalpha inhibits CD36 expression on human monocytes, while adalimumab independently upregulates it.
• These findings highlight the complex interplay between pro-inflammatory cytokines, their neutralization, and cellular receptors involved in atherosclerosis.
• Further research is needed to clarify the clinical implications for accelerated atherosclerosis in rheumatoid arthritis.