Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages

• Authors: Shangrila Parvin, Emory University; Clintoria R Williams, Emory University; Simone A Jarrett, Emory University; Sandra Garraway, Emory University
• Journal Title: INFLAMMATION
• Volume: Volume 44, Number 6
• Publisher: SPRINGER/PLENUM PUBLISHERS | 2021-08-21, Pages 2346-2361
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1007/s10753-021-01507-x
• Subjects: Biology, Cell; Biology, Physiology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cell Biology; Immunology; cytokines; c-fos; systemic inflammation; kidney; spinal cord injury; ACUTE-RENAL-FAILURE; NECROSIS-FACTOR-ALPHA; C-FOS EXPRESSION; NOXIOUS-STIMULATION; CELL-DEATH; AUTONOMIC DYSREFLEXIA; SECONDARY DAMAGE; CONTUSION INJURY; BLADDER FUNCTION; MACROPHAGES

Abstract

Accumulating evidence supports that spinal cord injury (SCI) produces robust inflammatory plasticity. We previously showed that the pro-inflammatory cytokine tumor necrosis factor (TNF)α is increased in the spinal cord after SCI. SCI also induces a systemic inflammatory response that can impact peripheral organ functions. The kidney plays an important role in maintaining cardiovascular health. However, SCI-induced inflammatory response in the kidney and the subsequent effect on renal function have not been well characterized. This study investigated the impact of high and low thoracic (T) SCI on C-fos, TNFα, interleukin (IL)-1β, and IL-6 expression in the kidney at acute and sub-chronic timepoints. Adult C57BL/6 mice received a moderate contusion SCI or sham procedures at T4 or T10. Uninjured mice served as naïve controls. mRNA levels of the proinflammatory cytokines IL-1β, IL-6, TNFα, and C-fos, and TNFα and C-fos protein expression were assessed in the kidney and spinal cord 1 day and 14 days post-injury. The mRNA levels of all targets were robustly increased in the kidney and spinal cord, 1 day after both injuries. Whereas IL-6 and TNFα remained elevated in the spinal cord at 14 days after SCI, C-fos, IL-6, and TNFα levels were sustained in the kidney only after T10 SCI. TNFα protein was significantly upregulated in the kidney 1 day after both T4 and T10 SCI. Overall, these results clearly demonstrate that SCI induces robust systemic inflammation that extends to the kidney. Hence, the presence of renal inflammation can substantially impact renal pathophysiology and function after SCI.