Rab7b participation on the TLR4 (Toll-like receptor) endocytic pathway in Shiga toxin-associated Hemolytic Uremic Syndrome (HUS).

Autor: Lafalla Manzano AF; Laboratorio de Citometría de Flujo, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina., Gil Lorenzo AF; Área de Fisiopatología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina., Bocanegra V; IMBECU-CONICET (Instituto de Medicina y Biología Experimental de Cuyo - Consejo Nacional de Investigaciones Científicas y Técnicas), Argentina., Costantino VV; IMBECU-CONICET (Instituto de Medicina y Biología Experimental de Cuyo - Consejo Nacional de Investigaciones Científicas y Técnicas), Argentina., Cacciamani V; IMBECU-CONICET (Instituto de Medicina y Biología Experimental de Cuyo - Consejo Nacional de Investigaciones Científicas y Técnicas), Argentina., Benardon ME; Área de Fisiopatología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina., Vallés PG; Área de Fisiopatología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina; IMBECU-CONICET (Instituto de Medicina y Biología Experimental de Cuyo - Consejo Nacional de Investigaciones Científicas y Técnicas), Argentina; Hospital Pediátrico Humberto J. Notti, Servicio de Nefrología, Ministerio de Salud, Mendoza, Argentina. Electronic address: pvalles@fcm.uncu.edu.ar.
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2019 Sep; Vol. 121, pp. 154732. Date of Electronic Publication: 2019 May 30.
DOI: 10.1016/j.cyto.2019.05.019
Abstrakt: Background: The inflammatory response of the host to Shiga toxin and/or lipopolysaccharide (LPS) of Escherichia coli (E. coli) is included in (HUS). The TLR4-LPS complex is internalized and TLR4 induced inflammatory signaling is stopped by targeting the complex for degradation. Rab7b, a small guanosine triphosphatase (GTPase) expressed in monocytes, regulates the later stages of the endocytic pathway.
Objective: we studied the Rab7b participation on the TLR4 endocytic pathway and its effect on monocyte cytokine production along the acute course of pediatric Shiga toxin-associated HUS.
Methods and Results: Monocytes were identified according to their positivity in CD14 expression. Surface TLR4 expression in monocytes from 18 HUS patients significantly increased by day 1 to 6, showing the highest increase on day 4 compared to monocytes of 10 healthy children. Significant higher surface TLR4 expression was accompanied by increased proinflammatory intracellular cytokines, tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). In contrast, after these time points, surface TLR4 expression and intracellular TNF-α levels, returned to near control levels after 10 days. Furthermore, confocal immunofluorescence microscopy proved colocalization of increased intracellular TLR4/Rab7b determined by Pearson's coefficient in monocytes from HUS patients from day 1 on the highest colocalization of both proteins by day 4. Decreased TLR4/Rab7b colocalization was shown 10 days after HUS onset.
Conclusion: The colocalization of TLR4 and Rab7b allows us to suggest Rab7b participation in the control of the TLR4 endocytic pathway in HUS patient monocytes. A consequential fall in cytokine production throughout the early follow up of HUS is demonstrated.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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