Stimulation of FcγRI on Primary Sensory Neurons Increases Insulin-Like Growth Factor-I Production, Thereby Reducing Reperfusion-Induced Renal Injury in Mice

Biological role(s) of Fc gammaRI on mouse primary sensory neurons are not fully understood. Sensory neuron stimulation increases insulin-like growth factor-I (IGF-I) production, thereby reducing ischemia/reperfusion (I/R)-induced tissue injury in mice. In this study, we examined whether the Fc fragment of IgG (IgGFc) increases IGF-I production through sensory neuron stimulation, thereby reducing I/R-induced renal injury in mice. IgGFc increased the calcitonin-gene-related peptide (CGRP) release and cellular cAMP levels in dorsal root ganglion neurons isolated from wild-type (WT) mice, whereas, native IgG did not. Pretreatment with anti-Fc gammaRI Ab, a protein kinase A inhibitor KT5710, and a phospholipase A(2) inhibitor 4-bromophenylacyl bromide inhibited these effects induced by IgGFc. Administration of IgGFc enhanced increases of renal tissue levels of CGRP and IGF-I and reduced I/R-induced renal injury in WT mice. Increases of renal tissue level of caspase-3, renal accumulation of neutrophils, and renal tubular apoptosis were inhibited by administration of IgGFc in WT mice subjected to renal I/R. Pretreatment with anti-IGF-I Ab completely reversed these effects induced by IgGFc in WT mice. Administration of native IgG did not show any effects in WT mice subjected to renal I/R. None of the effects observed in WT mice was seen after IgGFc administration in CGRP-knockout mice and denervated WT mice. These observations suggest that activation of Fc gammaRI by IgGFc may stimulate sensory neurons, thereby promoting IGF-I production, contributing to reduction of the reperfusion-induced renal injury via attenuation of inflammatory responses in mice.