Dysfunctional crosstalk between macrophages and fibroblasts under LPS-infected and hyperglycemic environment in diabetic wounds

High glucose levels significantly reduces macrophage phagocytic activity, hindering infection clearance and nitric oxide production. High glucose (with AGEs) inhibited the anti-inflammatory molecule IL-10. An increase in the chemokines production and higher expression of M1 markers indicate that under an LPS-infected and/or hyperglycemic environment, macrophages are recruited to the wound site. The presence of fibroblasts at the site plays an essential role in this process with dermal enhancement of cellular migration playing a critical role in the wound healing process. LPS alone did not change the levels of TNF-α and IL-6, which might be because IL1-β was not secreted excluding the possibility of its autocrine effect (Fig. 9). IL-8 production was significantly higher (P < 0.05) in the presence of high glucose ( with A GEs) and LPS. L PS-induction alone also promoted the production of MIP chemokine MIP-1α and Mip-1β. Chemokines RANTES and MCP-1 were significantly increased by high glucose.

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