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The Effects of Insulin-Like Growth Factor I and BTP-2 on Acute Lung Injury.
Munoz, Kevin; Wasnik, Samiksha; Abdipour, Amir; Bi, Hongzheng; Wilson, Sean M; Tang, Xiaolei; Ghahramanpouri, Mahdis; Baylink, David J.
  • Munoz K; Department of Medicine, Division of Regenerative Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
  • Wasnik S; Department of Medicine, Division of Regenerative Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
  • Abdipour A; Department of Medicine, Division of Regenerative Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
  • Bi H; Division of Nephrology, Loma Linda University Medical Center, Loma Linda, CA 92354, USA.
  • Wilson SM; Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China.
  • Tang X; The Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA.
  • Ghahramanpouri M; Department of Medicine, Division of Regenerative Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
  • Baylink DJ; Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, Long Island University, Brookville, NY 11548, USA.
Int J Mol Sci ; 22(10)2021 May 15.
Article in English | MEDLINE | ID: covidwho-1236794
ABSTRACT
Acute lung injury (ALI) afflicts approximately 200,000 patients annually and has a 40% mortality rate. The COVID-19 pandemic has massively increased the rate of ALI incidence. The pathogenesis of ALI involves tissue damage from invading microbes and, in severe cases, the overexpression of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). This study aimed to develop a therapy to normalize the excess production of inflammatory cytokines and promote tissue repair in the lipopolysaccharide (LPS)-induced ALI. Based on our previous studies, we tested the insulin-like growth factor I (IGF-I) and BTP-2 therapies. IGF-I was selected, because we and others have shown that elevated inflammatory cytokines suppress the expression of growth hormone receptors in the liver, leading to a decrease in the circulating IGF-I. IGF-I is a growth factor that increases vascular protection, enhances tissue repair, and decreases pro-inflammatory cytokines. It is also required to produce anti-inflammatory 1,25-dihydroxyvitamin D. BTP-2, an inhibitor of cytosolic calcium, was used to suppress the LPS-induced increase in cytosolic calcium, which otherwise leads to an increase in proinflammatory cytokines. We showed that LPS increased the expression of the primary inflammatory mediators such as toll like receptor-4 (TLR-4), IL-1ß, interleukin-17 (IL-17), TNF-α, and interferon-γ (IFN-γ), which were normalized by the IGF-I + BTP-2 dual therapy in the lungs, along with improved vascular gene expression markers. The histologic lung injury score was markedly elevated by LPS and reduced to normal by the combination therapy. In conclusion, the LPS-induced increases in inflammatory cytokines, vascular injuries, and lung injuries were all improved by IGF-I + BTP-2 combination therapy.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thiadiazoles / Insulin-Like Growth Factor I / Gene Expression Regulation / Cytokines / Acute Lung Injury / Anilides Type of study: Experimental Studies / Observational study / Prognostic study Topics: Long Covid Limits: Animals Language: English Year: 2021 Document Type: Article Affiliation country: Ijms22105244

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thiadiazoles / Insulin-Like Growth Factor I / Gene Expression Regulation / Cytokines / Acute Lung Injury / Anilides Type of study: Experimental Studies / Observational study / Prognostic study Topics: Long Covid Limits: Animals Language: English Year: 2021 Document Type: Article Affiliation country: Ijms22105244