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

PATRICIA KUNDA; JUAN CARLOS CAVICCHIA; CRISTIAN ACOSTA

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2014 vol. 280 p. 60 - 82

0306-4522

Binding of bacterial Lipopolisaccharydes (LPS) to Toll-like receptor 4 (TLR4) triggers an innate immunoresponse associated to pain and inflammation. The expression and regulation of the TLR4 and its auxiliary proteins are poorly understood in trigeminal and nodose neurons. We used a combination of Western Blot, semi-quantitative PCR, pharmacological manipulation and immunostaining to determine the expression pattern and regulation by LPS and trophic factors of TLR4/MD2/CD14 and RP105/MD1 in neonatal trigeminal and nodose mice neurons. We found that all these proteins were expressed in both trigeminal and nodose neurons. We demonstrated that the trophic factors Artemin and NGF upregulated MD2 and RP105 mRNA levels in trigeminal neurons, while CNTF, LIF and BDNF upregulated MD1 and also RP105 mRNA levels in nodose neurons. LPS acutely (within 20 mins) down regulated CD14 and MD2, but their mRNA levels recovered after 3 hrs. In addition, LPS increased significantly the proportion of Nociceptin/Orphanin FQ neurons in both trigeminal and nodose neurons in culture via TLR4/MD2. We conclude that LPS acts through its archetypical receptor in trigeminal and nodose neurons. In turn these receptor complexes are acutely regulated by LPS. Trophic factors also have a regulatory influence in the longer term. Thus, in sensory nodose and trigeminal neurons LPS may stimulate TLR4/MD2/CD14 and/or RP105/MD1 resulting in the common symptoms provoked by gram negative bacterial infections (e.g. fiber inflammation, pain, cough, toothache).