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Surfactant protein A (SP-A) plays an important role in innate immune response and host defense against various microorganisms through opsonization and complement activation. To investigate the role of SP-A in non-typeable Haemophilus influenzae (NTHi)-induced acute otitis media, this study used wild type C57BL/6 (WT) and SP-A knockout (KO) mice. We divided mice into an infection group in which the middle ear (ME) was injected with NTHi and a control group that received the same treatment using normal saline. Mice were sacrificed on d 1, 3, and 7 after treatment. Temporal bone samples were fixed for histological, cellular, and molecular analyses. Ear washing fluid (EWF) was collected for culture and analyses of pro-inflammatory cytokines and inflammatory cells. SP-A-mediated bacterial aggregation and killing and phagocytosis by macrophages were studied in vitro. SP-A expression was detected in the ME and Eustachian tube mucosa of WT mice but not KO mice. After infection, KO mice showed more severe inflammation evidenced by increased ME mucosal thickness and inflammatory cell infiltration and higher NF-κB activation compared to WT mice. The levels of IL-6 and IL-1β in the EWF of infected KO mice were higher compared to infected WT mice on d 1. Our studies demonstrated that SP-A mediated NTHi aggregation and killing and enhanced bacterial phagocytosis by macrophages in vitro and modulated inflammation of the ME in otitis media in vivo.
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1,25‐Dihydroxyvitamin D 3 and dietary vitamin D reduce inflammation in mice lacking intestinal epithelial cell Rab11a
Abstract A number of studies have examined the effects of 1,25‐dihydroxyvitamin D3(1,25(OH)2D3) on intestinal inflammation driven by immune cells, while little information is currently available about its impact on inflammation caused by intestinal epithelial cell (IEC) defects. Mice lacking IEC‐specificRab11aa recycling endosome small GTPase resulted in increased epithelial cell production of inflammatory cytokines, notably IL‐6 and early onset of enteritis. To determine whether vitamin D supplementation may benefit hosts with epithelial cell‐originated mucosal inflammation, we evaluated in vivo effects of injected 1,25(OH)2D3or dietary supplement of a high dose of vitamin D on the gut phenotypes of IEC‐specificRab11aknockout mice (Rab11aΔIEC). 1,25(OH)2D3administered at 25 ng, two doses per mouse, by intraperitoneal injection, reduced inflammatory cytokine production in knockout mice compared to vehicle‐injected mice. Remarkably, feeding mice with dietary vitamin D supplementation at 20,000 IU/kg spanning fetal and postnatal developmental stages led to improved bodyweights, reduced immune cell infiltration, and decreased inflammatory cytokines. We found that these vitamin D effects were accompanied by decreased NF‐κB (p65) in the knockout intestinal epithelia, reduced tissue‐resident macrophages, and partial restoration of epithelial morphology. Our study suggests that dietary vitamin D supplementation may prevent and limit intestinal inflammation in hosts with high susceptibility to chronic inflammation.
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- Award ID(s):
- 1952823
- PAR ID:
- 10305178
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Journal of Cellular Physiology
- Volume:
- 236
- Issue:
- 12
- ISSN:
- 0021-9541
- Page Range / eLocation ID:
- p. 8148-8159
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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