Yin and Yang: CCL2 and IL‐10 in Otitis Media‐induced Inner Ear Inflammation

Abstract

Otitis media (OM) may lead to inner ear inflammation resulting in sensorineural hearing loss. Here, we aim to determine the role of spiral ligament fibrocytes (SLFs)‐derived CCL2 and exogenous IL‐10 in inner ear inflammation, secondary to nontypeable H. influenzae (NTHI)‐induced OM. THP‐1 cells actively migrated in response to the conditioned medium of NTHI‐exposed SLFs. This migratory activity was inhibited by the CC chemokine inhibitor and by the deficiency of CCL2 in SLFs. The CCR2 inhibitor and CCR2 deficiency inhibited migration of monocyte‐like cells of the splenocytes in response to NTHI‐induced SLF‐derived CCL2. qRT‐PCR showed that recombinant IL‐10 inhibits SLF's NTHI‐induced up‐regulation of CCL2 expression. Luciferase assays showed that silencing of IL‐10RA in SLFs suppressed the inhibitory effect of IL‐10 on NTHI‐induced CCL2 up‐regulation. In contrast, IL‐10 deficiency of SLFs hardly affected NTHI‐induced CCL2 expression. Transtympanic inoculation of live NTHI led to inner ear inflammation in 10 out of 14 murine ears (71%). Unexpectedly, CCL2 deficiency equivocally decreased the incidence of OM‐induced inner ear inflammation (60%), indicating a compensatory effect of other chemokines in vivo. Taken together, we suggest that NTHI‐induced SLF‐derived CCL2 contributes to OM‐induced inner ear inflammation, which is negatively regulated by IL‐10. [Supported in part by DC008696 and DC006276]