TLR4 and Hyperglycemia: Other research has also shown elevated levels of TLRs, HMGB-1, and cytokines like TNF-α, IL-6, IL-1β, TGF-β1, ICAM-1, and MCP-1 in DN.74–77 Specifically, Lin and colleagues (2012), demonstrated increased expression of TLR-4 and HMGB-1 in renal tubules of individuals with diabetic nephropathy, with TLR-4 levels correlating with interstitial macrophage infiltration and glycosylated haemoglobin.78 Furthermore, hyperglycaemia induced TLR-4 expression via PKC, leading to elevated levels of IL-6 and CCL-2 through the IkB/NF-κB pathway.