Leptin Promotes Corneal Allograft Rejection In a Rat Model Via Enhancing Macrophage Activation And Cytokine Production
Research Square (Research Square)(2021)
Abstract
Obesity is closely related to exacerbated graft rejection and worse graft survival. High leptin levels, caused by excessive adipose cells in obese individuals, may exert a pivotal role in the pathogenesis of allograft rejection. However, the role and underlying mechanism of leptin in allograft rejection remains unclear. This study explored the role and potential mechanism of leptin in allograft rejection in rats. We performed allogeneic corneal transplantation in rats. The recipients were treated with subconjunctival injections of recombinant rat leptin after transplantation. Clinical evaluation, immunohistological assessment, real-time PCR and flow cytometry were administrated. RAW264.7 macrophages were handled with leptin (3 µg/mL) for 4 hours and then were treated with lipopolysaccharide (10ng/mL) for 24 hours. The culture supernatants were acquired for ELISA. NF-κBp65 activation in RAW264.7 macrophages was detected by western blot. Our results showed that the leptin-treated rats had a significantly reduced corneal graft mean survival time. The number of infiltrating F4/80+CD68+ macrophages increased in the leptin-treated corneal grafts. Monocyte chemoattractant protein-1(MCP-1), tumor necrosis factor-α (TNF-α) and interleukin 6(IL-6) mRNA expression level was higher in the leptin-treated corneal grafts than in the control allografts. Leptin treatment notably increased the frequency and number of T helper 1 (Th1) cells and T helper 17 (Th17) cells in rat ipsilateral cervical lymph nodes. Leptin enhanced NF-κBp65 activation and promoted MCP-1, TNF-α and IL-6 production in RAW264.7 macrophages. Leptin promoted corneal allograft rejection by enhancing the recruitment and activation of macrophages.
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Key words
macrophage
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