Dioleoylphosphatidylglycerol Inhibits Heat Shock Protein B4 (HSPB4)-Induced Inflammatory Pathways In Vitro.

Our previous work shows that dioleoylphosphatidylglycerol (DOPG) accelerates corneal epithelial healing in vitro and in vivo by unknown mechanisms. Prior data demonstrate that DOPG inhibits toll-like receptor (TLR) activation and inflammation induced by microbial components (pathogen-associated molecular patterns, PAMPs) and by endogenous molecules upregulated in psoriatic skin, which act as danger-associated molecular patterns (DAMPs) to activate TLRs and promote inflammation. In the injured cornea, sterile inflammation can result from the release of the DAMP molecule, heat shock protein B4 (HSPB4), to contribute to delayed wound healing. Here, we show in vitro that DOPG inhibits TLR2 activation induced in response to HSPB4, as well as DAMPs that are elevated in diabetes, a disease that also slows corneal wound healing. Further, we show that the co-receptor, cluster of differentiation-14 (CD14), is necessary for PAMP/DAMP-induced activation of TLR2, as well as of TLR4. Finally, we simulated the high-glucose environment of diabetes to show that elevated glucose levels enhance TLR4 activation by a DAMP known to be upregulated in diabetes. Together, our results demonstrate the anti-inflammatory actions of DOPG and support further investigation into its development as a possible therapy for corneal injury, especially in diabetic patients at high risk of vision-threatening complications.

Red crusty plaques in a young man.

Pemphigus foliaceus is a superficial blistering disorder characterized by erosions and scaling in a seborrheic distribution. The condition typically occurs in healthy individuals but issues arise from delayed diagnosis. Many cases remain undiagnosed or misdiagnosed due to the lack of awareness of the condition. With use of common diagnostic tools, pemphigus foliaceus can be easily identified and monitored. Histological analysis exhibits "chicken wire" patterning along keratinocytes in the upper epidermis, whereas immunofluorescence study displays subcorneal acantholysis. Pemphigus foliaceus is confirmed via ELISA studies revealing the presence of autoantibodies against desmoglein 1. Once correctly diagnosed, typically the condition is responsive to corticosteroid therapy. However in recalcitrant cases such as in ours, adjunctive immunosuppressive therapy with dapsone or rituximab may be indicated.