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Zip14 (Slc39A14) is critical to modulate inflammatory responses in murine skeletal muscle
Author(s) -
Kim Jinhee,
Aydemir Tolunay Beker,
Cousins Robert J.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.919.3
Subject(s) - skeletal muscle , inflammation , endocrinology , medicine , paracrine signalling , autocrine signalling , proinflammatory cytokine , cytokine , biology , chemistry , receptor
Skeletal muscle has primarily a contractile function that is accompanied with secretion of molecules that act through autocrine, paracrine, and endocrine modes of action. Some of these muscle‐derived factors are induced during inflammation. The cytokine IL‐6 is produced in muscle and responds to inflammation and endotoxemia induced by LPS (endotoxin). Zinc metabolism is altered during endotoxemia. In this context, specific zinc transporters respond to endotoxemia. Using LPS administration to mice, we identified that expression of a relatively few zinc transporter genes were up‐regulated in skeletal muscle after LPS. At the transcript level, Zip14, a transporter associated with cellular zinc uptake, was the most highly upregulated of all 24 zinc transporter mRNAs in response to LPS administration. LPS also altered the zinc concentration in skeletal muscle. We hypothesized that Zip14 plays an important role in muscle during inflammation such as IL‐6 production. To determine the potential role of muscle Zip14 during inflammation, we used female wild type (WT) and Zip14 KO mice administered LPS by intraperitoneal injection. Interestingly, TNFα and IL‐6 mRNA expression in skeletal muscle of Zip14 KO mice over time was greater than in WT mice. The increased IL‐6 production and concurrent activation of the NF‐kB pathway, which was greater in the Zip14 KO mice, is suggestive of a regulatory role of Zip14 in skeletal muscle during inflammation. Hence, Zip14 may be an important factor to control zinc homeostasis and metabolic signaling in skeletal muscle during inflammation, suggesting a strong correlation between Zip14 and cytokines with the innate immune system, host defense, chronic disease and aging. Support or Funding Information Supported by grant DK94244 from the National Institutes of Health.