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1.
Fig 9

Fig 9. From: Roles of STAT3 in Protein Secretion Pathways during the Acute-Phase Response.

Proposed model of STAT3 contributions to the acute-phase response elicited by pneumonia. During pneumonia, hepatocyte STAT3 is activated by IL-6 and also by ER stress resulting from the newly synthesized load of acute-phase proteins. STAT3 induces the expression of secretory pathway-related proteins, such as those in translocon, chaperone, and coat protein complexes, enhancing the extracellular delivery of the newly translated acute-phase proteins to mediate innate immunity in the bloodstream.

Ayele-Nati N. Ahyi, et al. Infect Immun. 2013 May;81(5):1644-1653.
2.
Fig 8

Fig 8. From: Roles of STAT3 in Protein Secretion Pathways during the Acute-Phase Response.

Secretory protein gene induction in other severe infections. Quantitative RT-PCR was performed on liver RNA collected from ICR mice subjected to CLP-induced sepsis (A) or C57BL/6 mice that received intratracheal instillations of E. coli (B). After 24 h, the livers were harvested for RNA extraction. Fold induction values for the indicated genes (compared to uninfected controls) are means ± standard errors of the means. *, P < 0.05 compared to uninfected mice (each panel represents a different experiment, each with 3 to 5 mice/group).

Ayele-Nati N. Ahyi, et al. Infect Immun. 2013 May;81(5):1644-1653.
3.
Fig 1

Fig 1. From: Roles of STAT3 in Protein Secretion Pathways during the Acute-Phase Response.

Secretory pathway gene induction during pneumococcal pneumonia. Quantitative RT-PCR was performed on liver RNA collected from B6/129 mice 0 to 24 h after intratracheal S. pneumoniae infection to evaluate transcripts involved in protein translation into the ER or vesicular transport to and from the ER. Values are the fold induction compared to uninfected controls and are expressed as means ± standard errors of the means. *, P < 0.05 compared to uninfected mice (results for one experiment, with 3 to 5 mice/group).

Ayele-Nati N. Ahyi, et al. Infect Immun. 2013 May;81(5):1644-1653.
4.
Fig 5

Fig 5. From: Roles of STAT3 in Protein Secretion Pathways during the Acute-Phase Response.

Expression of UPR target genes is diminished by STAT3 mutation. Stat3hepΔ mice and control (WT) littermates received intratracheal instillations of S. pneumoniae 24 h before the livers were harvested for RNA extraction. Quantitative RT-PCR analysis of UPR genes was performed. Fold induction values for the indicated genes are expressed as means ± standard errors of the means. *, P < 0.05 versus WT (results from 2 independent experiments, with a total of 9 or 10 mice/group for pneumonia and 3 mice/group for uninfected).

Ayele-Nati N. Ahyi, et al. Infect Immun. 2013 May;81(5):1644-1653.
5.
Fig 4

Fig 4. From: Roles of STAT3 in Protein Secretion Pathways during the Acute-Phase Response.

Secretory protein gene induction is unaffected by mutation of RelA. RelAhepΔ mice and control littermates received intratracheal instillations of S. pneumoniae 24 h before the livers were harvested for RNA extraction. Quantitative RT-PCR analysis of secretory protein genes in RelAhepΔ mouse liver RNA extracts was performed. Fold induction values for the indicated genes are expressed as means ± standard errors of the means. There were no significant effects of genotype for any gene (results from 3 independent experiments, with a total of 5 to 8 mice/group).

Ayele-Nati N. Ahyi, et al. Infect Immun. 2013 May;81(5):1644-1653.
6.
Fig 2

Fig 2. From: Roles of STAT3 in Protein Secretion Pathways during the Acute-Phase Response.

Secretory protein gene induction is diminished by simultaneous mutation of both STAT3 and RelA. Stat3/RelAhepΔ mice and control (WT) littermates received intratracheal instillations of S. pneumoniae 24 h before the livers were harvested for RNA extraction. Quantitative RT-PCR analysis of secretory protein genes in Stat3/RelAhepΔ mouse liver RNA extracts was performed. Fold induction values for the indicated genes are the means ± standard errors of the means. *, P < 0.05 versus WT (results from 2 independent experiments, with a total of 6 to 10 mice/group).

Ayele-Nati N. Ahyi, et al. Infect Immun. 2013 May;81(5):1644-1653.
7.
Fig 3

Fig 3. From: Roles of STAT3 in Protein Secretion Pathways during the Acute-Phase Response.

Secretory protein gene induction requires STAT3. Stat3hepΔ mice and control (WT) littermates received intratracheal instillations of S. pneumoniae 24 h before the livers were harvested for RNA extraction. Quantitative RT-PCR analysis of secretory protein genes in Stat3hepΔ mouse liver RNA extracts was performed. Fold induction values for the indicated genes are expressed as means ± standard errors of the means. *, P < 0.05 versus WT (results from 2 independent experiments, with a total of 9 to 10 mice/group for pneumonia and 3 mice/group for uninfected controls).

Ayele-Nati N. Ahyi, et al. Infect Immun. 2013 May;81(5):1644-1653.
8.
Fig 6

Fig 6. From: Roles of STAT3 in Protein Secretion Pathways during the Acute-Phase Response.

STAT3 mediates secretory protein gene induction elicited by ER stress. Stat3hepΔ mice and control (WT) littermates received intraperitoneal injections of tunicamycin 24 h before the livers were harvested for RNA or protein extraction. (A) Western blot analysis of total and phospho-STAT3, using total liver protein extract. Each lane contains an extract from a different mouse. (B) Quantitative RT-PCR results for secretory protein genes in STAT3hepΔ mice, based on liver RNA extracts. Fold induction values for the indicated genes are means ± standard errors of the mean. *, P < 0.05 compared to WT (results from 2 independent experiments, with a total of 4 to 8 mice/group).

Ayele-Nati N. Ahyi, et al. Infect Immun. 2013 May;81(5):1644-1653.
9.
Fig 7

Fig 7. From: Roles of STAT3 in Protein Secretion Pathways during the Acute-Phase Response.

Phosphorylated STAT3 binds to secretory protein gene promoters during pneumonia. (A) Schematics of Arfgap3 and Grp78 promoter loci, with putative STAT3-binding sites shown as hash marks on the scaled diagram of the 2,000-bp promoter region and positioned relative to the transcriptional start site. Putative STAT3-binding sites were identified using the TRANSFAC databases, and all sites with a core score greater than 0.99 and matrix score greater than 0.7 (matrix library; TRANSFAC matrix table; release 2012.2) are noted by a hash mark. The locations of the primers used for quantitative PCR are represented by 2 opposing arrows, and positions relative to the transcriptional start site are indicated. The translational start is depicted by a bent arrow. (B) ChIP results with phosphorylated STAT3 revealed a pneumonia-induced association with proximal promoter regions of secretory protein genes. Chromatin was isolated from liver cells collected from C57BL/6 mice 0 or 24 h after S. pneumoniae pneumonia infection, fixed, sheared, and immunoprecipitated with antibodies against phosphorylated STAT3. Precipitated 200- to 600-bp DNA fragments containing the regions amplified were measured using quantitative PCR. Fold induction values for the indicated genes were calculated relative to values observed in uninfected mice (dashed line) and are expressed as means ± standard error of the means. *, P < 0.05 versus distal promoter region (n = 3 mice/group).

Ayele-Nati N. Ahyi, et al. Infect Immun. 2013 May;81(5):1644-1653.

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