Key result
IL-10 knockout mice exhibited diminished estrogen signaling and defective bone mineralization, leading to an approximate 4-fold increase in FGF23 that contributed to cardiac fibrosis.
Why the study?
The role of IL-10 in cross-talk between gut inflammation, cardiovascular dysfunction, and bone loss was not fully understood.
Effect estimate: ~4-fold increase
p-value: p=<0.05
In a mouse model, IL-10 deficiency leads to reduced estrogen signaling and defective bone mineralization, which increases FGF23 and contributes to cardiac fibrosis.
Characterization of the interleukin (IL)‐10 knockout (KO) mouse with chronic gut inflammation, cardiovascular dysfunction, and bone loss suggests a critical role for this cytokine in interorgan communication within the gut, bone, and cardiovascular axis. We sought to understand the role of IL‐10 in the cross‐talk between these systems. Six‐week‐old IL‐10 KO mice and their wild type (WT) counterparts were maintained on a standard rodent diet for 3 or 6 months. Gene expression of proinflammatory markers and Fgf23 , serum 17β‐estradiol (E2), and cardiac protein expression were assessed. Ileal Il17a and Tnf mRNA increased while Il6 mRNA increased in the bone and heart by at least 2‐fold in IL‐10 KO mice. Bone Dmp1 and Phex mRNA were repressed at 6 months in IL‐10 KO mice, resulting in increased Fgf23 mRNA (~4‐fold) that contributed to increased fibrosis. In the IL‐10 KO mice, gut bacterial β‐glucuronidase activity and ovarian Cyp19a1 mRNA were lower ( p < 0.05), consistent with reduced serum E2 and reduced cardiac pNOS3 (Ser 1119 ) in these mice. Treatment of ileal lymphocytes with E2 reduced gut inflammation in WT but not IL‐10 KO mice. In conclusion, our data suggest that diminished estrogen and defective bone mineralization increased FGF23 which contributed to cardiac fibrosis in the IL‐10 KO mouse.
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Alake et al. (2024) studied Interleukin-10 deficiency (chronic gut inflammation, cardiovascular dysfunction, and bone loss). Interleukin-10 knockout vs. Wild-type mice was evaluated on Fgf23 mRNA expression and cardiac fibrosis (~4-fold increase, p=<0.05). IL-10 knockout mice exhibited diminished estrogen signaling and defective bone mineralization, leading to an approximate 4-fold increase in FGF23 that contributed to cardiac fibrosis.
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