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. 2017 May 16;8:15433. doi: 10.1038/ncomms15433

Figure 5. Identification of secreted factor(s) mediating non-cell-autonomous activation of STAT3 by FGF19.

Figure 5

(a) Hepatic IL-6 mRNA is induced in FGF19-treated db/db mice. 11∼12-week old db/db mice received an intraperitoneal injection of 1 mg kg−1 FGF19 or vehicle (V), and livers were harvested 2 h post dose (n=5 per group). (b) Lack of induction of canonical pSTAT3-activating cytokines, such as IL-11, LIF, OSM, CNTF and CTF-1, in FGF19-treated mice. (c) Lack of induction of additional pSTAT3-activating growth factors and cytokines, such as EGF, IL-10, IL-21, IL-22 and IL-31, in FGF19-treated mice. (d) Suppression of hepatic Cyp7a1 mRNA in FGF19-treated mice. (e) Blocking antibody against mouse IL-6 abolishes pSTAT3Y705 activation by FGF19. 11–12-week old db/db mice were injected intraperitoneally with a neutralizing anti-IL-6 antibody before FGF19 administration, and livers were harvested 2 h post FGF19 dose (n=3 per group). (f) Intracellular IL-6 cytokine staining of non-parenchymal cells analysed by flow cytometry. Representative forward scatter (FSC) and side scatter (SSC) plot of ungated cells is shown. Live cells were identified based on Live/Dead-DAPI staining (L/D). IL-6-positive cell gate (IL-6+) was used for subsequent analysis. (g) Co-localization of IL-6 with markers of myeloid cells (CD11b+), Kupffer cells (F4/80+), neutrophils (Ly6G+), NK cells (NK1.1+), but not T cells (CD3+) or B cells (CD19+). (h) Depletion of Kupffer cells reduces pSTAT3Y705 activation by FGF19. 11–12-week old db/db mice (n=4 per group) were injected intravenously with clodronate liposomes (to deplete Kupffer cells) or PBS liposomes. Livers were harvested 2 h post 1 mg kg−1 FGF19 dose. Values are mean±s.e.m. ***P<0.001 by unpaired, two-tailed t-test.