Fig. 4

OLDA upregulates circulating IL-10 in endotoxemic mice via TRPV1-expressing neurons of the central nervous system. A OLDA induces IL-10 via neuronal TRPV1: A1 Baf53b-Cre^+/−/TRPV1^lox/lox mice had reduced brain and DRG TRPV1 gene expression. ^#For DRG qPCR, each dot represents a pool from 1–2 animals. A2 Baf53b-Cre^±/ TRPV1^lox/lox mice had attenuated responses to heat-sensitivity testing (8- to 12-week female mice). A3 Pan-neuronal TRPV1 knockdown in Baf53b-Cre^+/−/TRPV1^lox/lox mice fully abrogated the upregulation of IL-10 and the downregulation of IL-6 induced by OLDA (10 mg/kg, i.v.) in mice treated with LPS (1 mg/kg, i.v.) (12-week male, n = 11–14/group). B OLDA does not act via PNS TRPV1; B1 Adv Cre^+/−/TRPV1^lox/lox mice had reduced TRPV1 expression in their DRG but not their brains. ^#For DRG qPCR, each dot represents a pool from 1–2 animals. B2 Adv Cre^+/−/TRPV1^lox/lox mice displayed attenuated responses to heat-sensitivity testing (8- to 12-week female mice). B3–B4 Calcium imaging shows a decreased percentage of capsaicin-responsive neurons in DRG neurons Adv Cre^+/−/TRPV1^lox/lox compared to Adv Cre^−/−/TRPV1^lox/lox and wild-type mice, and longer onset response time (n = 3 mice/group; number of neurons imaged = 19–31 neurons/genotype). B5 Peripheral neuron TRPV1 knockdown in Adv Cre^+/−/TRPV1^lox/lox mice did not abrogate the IL-10 upregulation or IL-6 downregulation induced by OLDA (10 mg/kg, i.v.) in mice treated with LPS (1 mg/kg, i.v.) (10- to 12-week male and female, n = 10–12/group). For all panels, *P < 0.05, **P < 0.01, ***P < 0.001, two-tailed Mann–Whitney U test