Abstract
BackgroundInnate immunity and tissue proliferation play important roles in otitis media (OM), the most common disease of childhood. CJUN terminal kinase (JNK) is potentially involved in both processes.ResultsGenes involved in both innate immune and growth factor activation of JNK are upregulated during OM, while expression of both positive and negative JNK regulatory genes is altered. When compared to wildtypes (WTs), C57BL/6 mice deficient in JNK1 exhibit enhanced mucosal thickening, with delayed recovery, enhanced neutrophil recruitment early in OM, and delayed bacterial clearance. In contrast, JNK2−/− mice exhibit delayed mucosal hyperplasia that eventually exceeds that of WTs and is slow to recover, delayed recruitment of neutrophils, and failure of bacterial clearance.ConclusionsThe results suggest that JNK1 and JNK2 play primarily opposing roles in mucosal hyperplasia and neutrophil recruitment early in OM. However, both isoforms are required for the normal resolution of middle ear infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-014-0046-z) contains supplementary material, which is available to authorized users.
Highlights
Innate immunity and tissue proliferation play important roles in otitis media (OM), the most common disease of childhood
Knockout experiments were performed on mice systemically deficient in JNK1 or JNK2 on a C57BL/6 background, and upon C57BL/6 WT controls, since they were produced on this background
Jnk1 and Jnk2 were modestly enhanced during middle ear (ME) infection
Summary
Innate immunity and tissue proliferation play important roles in otitis media (OM), the most common disease of childhood. Activated JNK phosphorylates members of the JUN family of proteins, including CJUN, JUNB, JUND, as well as ATF2. Phosphorylated CJUN homodimerizes or forms heterdimers with phosphorylated FOS or ATF2, to form the AP-1 transcriptional activator, which can potentially regulate many genes [11,12]. Growth factor binding to their cognate receptors recruit adaptors, including SHC, GRB and SOS, can activate the small GTPases KRAS, and CDC42 [13], which in turn activate MAPK kinase kinase kinases (MAP3Ks) 1 and 4. These converge with TLR signaling by activating MAP2Ks 4 and 7 to, in turn, phosphorylate JNK
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