Immunomodulation by vanilloids and the transient receptor potential vanilloid 1 (TRPV1)

In 2014 we reported that N-arachidonoyl dopamine (NADA), an endogenous lipid that activates the vanilloid receptor, TRPV1, reduces pro-inflammatory cytokine production by human endothelial cells and leukocytes induced by bacterial lipopolysaccharide (LPS), bacterial lipopeptide, and TNF⍺. Subsequently we found that NADA, and another vanilloid, N-oleoyl dopamine (OLDA) have strong anti-inflammatory effects in vivo in endotoxemic mice and in mice with bacterial sepsis. Both OLDA and NADA upregulate blood levels of IL-10, an anti-inflammatory cytokine, while decreasing multiple pro-inflammatory cytokines (e.g., IL-6, CCL2, IL-1b). We determined that the anti-inflammatory actions of OLDA and NADA are mediated by transient receptor potential vanilloid 1 (TRPV1), and recently discovered that TRPV1 expressed by neurons mediates the ant-inflammatory effects of OLDA. TRPV1 is well known for its roles in regulating pain and thermosensation. 

Current Projects on the vanilloids and TRPV1

1. Determining the immunomodulatory effects and mechanisms of action of NADA and OLDA. 
2. Characterizing the effects of OLDA and NADA on inflammatory and functional outcomes of bacterial sepsis and acute inflammation. 
3. Defining the effects of bacterial sepsis on levels of NADA and OLDA in the circulation and in neuronal tissues.  
4. Defining the role of IL-10 upregulation induced by NADA and OLDA in directing functional outcomes of sepsis and, acute inflammation.