Surfactant protein D (SP-D) is a C-type collectin and plays an important role in innate immunity and homeostasis in the lung. This study studied SP-D role in the nontypeable Haemophilus influenzae (NTHi)-induced otitis media (OM) mouse model. Wild-type C57BL/6 (WT) and SP-D knockout (KO) mice were used in this study. Mice were injected in the middle ear (ME) with 5 μL of NTHi bacterial solution (3.5 × 105 CFU/ear) or with the same volume of sterile saline (control). Mice were sacrificed at 3 time points, days 1, 3, and 7, after treatment. We found SP-D expression in the Eustachian tube (ET) and ME mucosa of WT mice but not in SP-D KO mice. After infection, SP-D KO mice showed more intense inflammatory changes evidenced by the increased mucosal thickness and inflammatory cell infiltration in the ME and ET compared to WT mice (p < 0.05). Increased bacterial colony-forming units and cytokine (IL-6 and IL-1β) levels in the ear washing fluid of infected SP-D KO mice were compared to infected WT mice. Molecular analysis revealed higher levels of NF-κB and NLRP3 activation in infected SP-D KO compared to WT mice (p < 0.05). In vitro studies demonstrated that SP-D significantly induced NTHi bacterial aggregation and enhanced bacterial phagocytosis by macrophages (p < 0.05). Furthermore, human ME epithelial cells showed a dose-dependent increased expression of NLRP3 and SP-D proteins after LPS treatment. We conclude that SP-D plays a critical role in innate immunity and disease resolution through enhancing host defense and regulating inflammatory NF-κB and NLRP3 activation in experimental OM mice.
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Astragaloside IV alleviates lipopolysaccharide‐induced preeclampsia‐like phenotypes via suppressing the inflammatory responses
Preeclampsia (PE) is a major cause of perinatal and maternal mortality and morbidity, which affects 2% to 8% of pregnancies in the world. The aberrant maternal inflammation and angiogenic imbalance have been demonstrated to contribute to the pathogenesis of PE. This research aimed to investigate the effect of Astragaloside IV (AsIV) in the treatment of PE and the underlying mechanisms. A rat PE‐like model was established by tail vein injection of lipopolysaccharide (LPS) and different doses of AsIV (40 and 80 mg/kg) were treated at the same time. Systolic blood pressure, total urine protein and urine volume were observed. Serum and placenta inflammatory cytokines were measured by ELISA kit. The mRNA and protein expression of relative genes were analyzed by qRT‐PCR and Western blotting. In PE‐like rats, there were obvious increases in systolic blood pressure, total urine protein and urine volume, which were obviously alleviated by treatment with AsIV. Serum levels of interleukin (IL)‐1β, tumor necrosis factor alpha (TNF‐α), IL‐6 and IL‐18, as well as IL‐4, IL‐10, PIGF, VEGF and sFlt‐1, were all reversed by treatment with AsIV. Meanwhile, AsIV treatment improved abnormal pregnancy outcomes, such as low litter size and low fetal weight. In addition, AsIV treatment downregulated the mRNA expression of inflammatory gene IL‐1β and IL‐6 in PE rats model, and AsIV treatment inhibited the activation of TLR‐4, NF‐κB, and sFlt‐1 in the placenta of PE rats. Our findings indicated the first evidence that AsIV alleviated PE‐like signs, and this improvement effect is possibly through inhibition of inflammation response via the TLR4/NF‐κB signaling pathway.
more » « less- NSF-PAR ID:
- 10453154
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- The Kaohsiung Journal of Medical Sciences
- Volume:
- 37
- Issue:
- 3
- ISSN:
- 1607-551X
- Page Range / eLocation ID:
- p. 236-244
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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