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Expression of suppressor of cytokine signalling 3 (SOCS3) in human bladder epithelial cells infected with uropathogenic Escherichia coli
Örebro universitet, Institutionen för hälsovetenskap och medicin.
School of Natural Sciences, Linnaeus University, Kalmar, Sweden.
Örebro universitet, Institutionen för hälsovetenskap och medicin.
Örebro universitet, Institutionen för hälsovetenskap och medicin.
2013 (Engelska)Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, nr 2, s. 158-167Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Suppressor of cytokine signalling (SOCS) proteins inhibit pro-inflammatory signalling mediated by Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathways. To evade the immune response some pathogens appear to modify the host SOCS proteins. Uropathogenic Escherichia coli (UPEC) are able to subvert the host response evoked by bladder epithelial cells, but the mechanisms are not fully understood. The objective of this study was to investigate whether UPEC can modify the host SOCS and STAT3 response. Real time RT-PCR studies demonstrated an increased SOCS1 and SOCS3 expression in the isolated human bladder epithelial cell lines (RT-4 and 5637) in response to cytokines. UPEC strain IA2 increased SOCS3, but not SOCS1, mRNA levels with a peak at 6 h after infection. The increase of SOCS3 was confirmed at the protein level by Western blotting. The UPEC strain IA2 caused a time-dependent decrease in the phosphorylation of STAT3. This study demonstrates that UPEC are able to affect SOCS3 and STAT3 signalling in human uroepithelial cells. The finding that UPEC are able to induce mediators involved in suppression of host cytokine signalling may help to elucidate how UPEC may circumvent the host response during urinary tract infection.

Ort, förlag, år, upplaga, sidor
Wiley-Blackwell, 2013. Vol. 121, nr 2, s. 158-167
Nationell ämneskategori
Medicin och hälsovetenskap
Forskningsämne
Medicin
Identifikatorer
URN: urn:nbn:se:oru:diva-26375DOI: 10.1111/j.1600-0463.2012.02951.xISI: 000313830700010PubMedID: 23030674OAI: oai:DiVA.org:oru-26375DiVA, id: diva2:565400
Anmärkning

Funding Agency:

Swedish Medical Research Council 65X-12601-11 

Faculty of Medicine and Health at Örebro University 

Tillgänglig från: 2012-11-07 Skapad: 2012-11-07 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
Ingår i avhandling
1. Uropathogenic Esherichia coli, multidrug-resistance and induction of host defense mechanisms
Öppna denna publikation i ny flik eller fönster >>Uropathogenic Esherichia coli, multidrug-resistance and induction of host defense mechanisms
2014 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Uropathogenic Escherichia coli (UPEC) is the primary cause of urinary tract infection (UTI), which is one of the most common infections in humans. UPEC strains have acquired successful strategies to subvert the host defense and antibiotics to persist in the urinary tract. The main aim of this thesis was to investigate the host defense mechanisms during a UPEC infection in vitro.

The results showed that SOCS3, a key regulator of the immune system, was increased in bladder epithelial cells in response to a UPEC infection. In addition, UPEC decreased the phosphorylation of the SOCS3 regulated transcription factor STAT3. Nitric oxide (NO), a host-derived antimicrobial factor was shown to increase the release of IL-6 from renal epithelial cells alone or in combination with UPEC. The induction of IL-6 was mediated by ERK1/2 and p38 MAPK signaling and NO was also shown to attenuate UPEC-induced IL-6 mRNA degradation. Furthermore, extended-spectrum beta-lactamase (ESBL)-producing UPEC isolates were shown to induce higher PMN migration and ROS-production, but lower cytokine secretion from renal epithelial cells than susceptible isolates. Ineffective ceftibuten treatment of ESBL isolates induced bacterial filamentation associated with an increased release of ATP and LPS, with a subsequent enhancement of the ESBL evoked host response.

Taken together, the findings show that UPEC can induce SOCS3, a suppressor of host responses and that NO can regulate proinflammatory mediators. In addition, the data suggest that there are differences between ESBL- and non-ESBL-producing isolates ability to evoke a host response. Exposing resistant isolates to ineffective antibiotics was shown to alter the evoked host response.

Ort, förlag, år, upplaga, sidor
Örebro: Örebro universitet, 2014. s. 87
Serie
Örebro Studies in Medicine, ISSN 1652-4063 ; 105
Nyckelord
Urinary tract infection, uropathogenic Escherichia coli, suppressor of cytokine signalling 3, nitric oxide, cytokines, extended-spectrum beta-lactamases, filamentation, IL-6
Nationell ämneskategori
Medicin och hälsovetenskap
Forskningsämne
Biomedicin
Identifikatorer
urn:nbn:se:oru:diva-33556 (URN)978-91-7529-013-3 (ISBN)
Disputation
2014-05-23, Campus USÖ (Universitetssjukhuset) X-huset, Hörsal C1, Södra Grev Rosengatan, 703 62 Örebro, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2014-02-04 Skapad: 2014-02-04 Senast uppdaterad: 2017-10-17Bibliografiskt granskad

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Demirel, IsakKruse, RobertPersson, Katarina

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