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001-es BibID:BIBFORM077162
035-os BibID:(WoS)000457627800001 (Scopus)85062188852 (cikkazonosító)131
Első szerző:Zarjou, Abolfazl (kutató orvos)
Cím:Ferritin Light Chain Confers Protection Against Sepsis-Induced Inflammation and Organ Injury / Zarjou Abolfazl, Black Laurence M., McCullough Kayla R., Hull Travis D., Esman Stephanie K., Boddu Ravindra, Varambally Sooryanarayana, Chandrashekar Darshan S., Feng Wenguang, Arosio Paolo, Poli Maura, Balla Jozsef, Bolisetty Subhashini
Dátum:2019
ISSN:1664-3224
Megjegyzések:Despite the prevalence and recognition of its detrimental impact, clinical complications of sepsis remain a major challenge. Here, we investigated the effects of myeloid ferritin heavy chain (FtH) in regulating the pathogenic sequelae of sepsis. We demonstrate that deletion of myeloid FtH leads to protection against lipopolysaccharide-induced endotoxemia and cecal ligation and puncture (CLP)-induced model of sepsis as evidenced by reduced cytokine levels, multi-organ dysfunction and mortality. We identified that such protection is predominantly mediated by the compensatory increase in circulating ferritin (ferritin light chain; FtL) in the absence of myeloid FtH. Our in vitro and in vivo studies indicate that prior exposure to ferritin light chain restrains an otherwise dysregulated response to infection. These findings are mediated by an inhibitory action of FtL on NF-?B activation, a key signaling pathway that is implicated in the pathogenesis of sepsis. We further identified that LPS mediated activation of MAPK pathways, specifically, JNK, and ERK were also reduced with FtL pre-treatment. Taken together, our findings elucidate a crucial immunomodulatory function for circulating ferritin that challenges the traditional view of this protein as a mere marker of body iron stores. Accordingly, these findings will stimulate investigations to the adaptive nature of this protein in diverse clinical settings.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
ferritin
inflammatory response
sepsis
NF-B, cytokine
LPS
multi-organ injury
myeloid cells
Megjelenés:Frontiers in Immunology. - 10 (2019), p. 1-15. -
További szerzők:Black, Laurence M. McCullough, Kayla R. Hull, Travis D. Esman, Stephanie K. Boddu, Ravindra Varambally, Sooryanarayana Chandrashekar, Darshan S. Feng, Wenguang Arosio, Paolo Poli, Maura Balla József (1959-) (belgyógyász, nephrológus) Bolisetty, Subhashini
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