Lipopolysaccharides and trophic factors regulate the LPS receptor complex in nodose and trigeminal neurons

KUNDA, PATRICIA; CAVICCHIA, JUAN; ACOSTA, CRISTIAN

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2014

0306-4522

Binding of bacterial Lipopolysaccharides (LPS) to Toll-like receptor 4 (TLR4) triggers aninnate immunoresponse associated with pain and inflammation. The expression, and to a greaterextent the regulation of TLR4 and its auxiliary proteins (MD1, MD2 and CD14), are both poorlyunderstood in trigeminal and nodose neurons.We used a combination of Western Blotting, semi-quantitative PCR, pharmacological manipulation andimmunohistochemistry. The expression pattern and regulation by LPS and trophic factors ofTLR4/MD2/CD14 and RP105/MD1 were determined in neonatal trigeminal and nodose mice neurons.We found that all these proteins were expressed in both trigeminal and nodose neurons. The trophicfactors Artemin and NGF up-regulated MD2 and RP105 mRNA levels in trigeminal neurons. In nodoseneurons the trophic factors BDNF, CNTF and LIF up-regulated MD1 and RP105 mRNA levels. Also weobserved that in both neuronal types LPS acutely (within 20 mins) down-regulated CD14 and MD2mRNAs. In addition, LPS increased significantly the proportion of trigeminal and nodose neuronsexpressing Nociceptin/Orphanin FQ in culture probably acting via TLR4/MD2.Although the exact mechanisms underlying the regulation by trophic factors and LPS require furtherelucidation, the findings of this study indicate that LPS acts through its archetypical receptor intrigeminal and nodose neurons.