title: Stimulation of Fc gammaRI on primary sensory neurons increases insulin-like growth factor-I production, thereby reducing reperfusion-induced renal injury in mice.
abstract: 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.
authors.affiliation: Department of Translational Medical Science Research, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Naoaki
authors.initials: N
authors.lastname: Harada
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurihara
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakagata
authors.forename: Kenji
authors.initials: K
authors.lastname: Okajima
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D017452:Receptors, IgG / Q000276:immunology*; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D000906:Antibodies; D002227:Carbazoles; C485701:Fcgr1 protein, mouse; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D064801:Phospholipase A2 Inhibitors; D011758:Pyrroles; D017452:Receptors, IgG; C057416:KT 5720; D007334:Insulin-Like Growth Factor I; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D054467:Phospholipases A2; D053148:Caspase 3; D015740:Calcitonin Gene-Related Peptide; C006821:4-bromophenacyl bromide