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Burn Injury Alters Cardiac β‐Adrenergic Receptor Signaling in Interleukin 6 Knockout Mice
Author(s) -
Guillory Ashley N,
El Ayadi Amina,
Porter Craig,
Herndon David N,
Finnerty Celeste C
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.719.14
Subject(s) - knockout mouse , burn injury , endocrinology , medicine , signal transduction , proinflammatory cytokine , receptor , phosphorylation , inflammation , biology , microbiology and biotechnology , surgery
Burn injury disrupts many signaling pathways including those that are β‐adrenergic receptor (β 1 ‐AR) dependent. Studies performed in various animal models have shown that burn injury causes cardiac dysfunction primarily attributed to altered β‐AR and pro‐inflammatory signaling. Interleukin 6 is involved in the regulation of cardiac hypertrophy as well as the development of heart failure, both of which are also regulated by β‐ARs. Methods Male wild‐type and interleukin 6 knockout mice received a 30% total body surface area full thickness burn. Animals were sacrificed and hearts were isolated 10 days post injury. We examined the expression of β‐ARs and downstream proteins via Western blotting. Protein kinase A activity was measured in cytosolic fractions using an enzyme immunoassay kit. Results β 1 ‐AR protein expression was significantly higher in the knockout animals after burn injury (p=0.01). Protein kinase A activity and Troponin I phosphorylation were also significantly higher in the interleukin 6 knockout mice post burn (p=0.003; 0.03). Conversely, β 2 ‐AR protein expression was significantly lower in the burned knockout animals (p=0.03). Sarcoplasmic reticulum calcium ATPase protein expression was significantly lower in both the wild‐type and interleukin 6 knockout mice after burn injury (p=0.003). Conclusion These data indicate that interleukin 6 may play a role in the disruption of cardiac β‐AR signaling including proteins involved in calcium handling after burn injury. Burn induced cardiac dysfunction has been well documented but is not clearly understood. Understanding how these signaling pathways are altered post injury may provide insight to the appropriate method of treatment. Support or Funding Information External Funding: Shriners Hospitals for Children (84291,80500, 84202,71008); National Institutes of Health (R01GM056687, R01HD049471‐07, R01AR065270, R01GM112936)