Skeletal muscle fibers play a functional role in host defense during sepsis in mice.
Skeletal muscle fibers play a functional role in host defense during sepsis in mice.
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DOI：
10.1038/s41598-021-86585-5
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发表时间：
2021-04-01
影响因子：
4.6
通讯作者：
Clanton TL
中科院分区：
文献类型：
--
作者：
Laitano O;Robinson GP;Murray KO;Garcia CK;Mattingly AJ;Morse D;King MA;Iwaniec JD;Alzahrani JM;Clanton TL
骨骼肌分泌多种免疫活性细胞因子，但这种应答对体内先天免疫的功能意义尚不清楚。我们通过敲除骨骼肌纤维中的Toll受体衔接蛋白Myd 88（skmMyd 88 KO）来解决这一问题，并在腹膜注射盲肠浆液（CS）（多微生物败血症模型）后6小时和12小时对雄性和雌性小鼠进行了随访。由于先前确定的CS注射死亡率增加，雄性动物接受的剂量降低约30%。在12 h时，与品系匹配的对照组相比，skmMyd 88 KO在雄性和雌性动物中引起多种促炎和抗炎血浆细胞因子（例如TNFα、IL-1β和IL-10）显著降低。在6 h时，在雌性动物中观察到类似的降低。在雌性CS后6和12 h，SkmMyd 88 KO导致腹膜中性粒细胞升高约40-50%。CS后12 h，skmMyd 88 KO增加了雌性动物的腹膜单核细胞/巨噬细胞，并降低了嗜酸性粒细胞%和嗜碱性粒细胞%。SkmMyd 88 KO也导致雌性小鼠的死亡率显著升高，但在雄性小鼠中没有。总之，结果表明，骨骼肌Myd 88依赖的信号转导可以发挥功能上的重要作用，在正常的全身，先天免疫炎症反应，腹腔脓毒症。
Skeletal muscles secrete a wide variety of immunologically active cytokines, but the functional significance of this response to in vivo innate immunity is not understood. We addressed this by knocking out the toll receptor adapter protein, Myd88, only in skeletal muscle fibers (skmMyd88KO), and followed male and female mice at 6 and 12 h after peritoneal injection of cecal slurry (CS), a model of polymicrobial sepsis. Because of a previously identified increase in mortality to CS injection, males received ~ 30% lower dose. At 12 h, skmMyd88KO caused significant reductions in a wide variety of pro- and anti-inflammatory plasma cytokines, e.g. TNFα, IL-1β and IL-10, compared to strain-matched controls in both males and females. Similar reductions were observed at 6 h in females. SkmMyd88KO led to ~ 40–50% elevations in peritoneal neutrophils at 6 and 12 h post CS in females. At 12 h post CS, skmMyd88KO increased peritoneal monocytes/macrophages and decreased %eosinophils and %basophils in females. SkmMyd88KO also led to significantly higher rates of mortality in female mice but not in males. In conclusion, the results suggest that skeletal muscle Myd88-dependent signal transduction can play functionally important role in normal whole body, innate immune inflammatory responses to peritoneal sepsis.
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影响因子：
32.4
作者：
Kawai, T;Adachi, O;Akira, S
通讯作者：
Akira, S
DOI：
10.1152/ajplung.00264.2010
发表时间：
2011-02-01
影响因子：
4.9
作者：
Gilliam, Laura A. A.;Moylan, Jennifer S.;Reid, Michael B.
通讯作者：
Reid, Michael B.
他莫昔芬通过调节细胞内神经酰胺来增强中性粒细胞的先天免疫功能。
影响因子：
16.6
作者：
Corriden R;Hollands A;Olson J;Derieux J;Lopez J;Chang JT;Gonzalez DJ;Nizet V
通讯作者：
Nizet V
DOI：
10.1164/rccm.201201-0134oc
发表时间：
2012-08-01
影响因子：
24.7
作者：
Linch, Stefanie N.;Danielson, Erin T.;Gold, Jeffrey A.
通讯作者：
Gold, Jeffrey A.
影响因子：
16.6
作者：
Buscher, Konrad;Wang, Huiyu;Song, Jian
通讯作者：
Song, Jian