کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1904507 1534639 2015 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Unsaturated but not saturated fatty acids induce transcriptional regulation of CCL2 in pancreatic acini. A potential role in acute pancreatitis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Unsaturated but not saturated fatty acids induce transcriptional regulation of CCL2 in pancreatic acini. A potential role in acute pancreatitis
چکیده انگلیسی


• Palmitic and stearic acids do not change the CCL2 expression in pancreatic acini.
• The unsaturated fatty acids (UFAs) oleic and linoleic up-regulate CCL2 in acini.
• MAPKs and JAK act as upstreams in the acinar CCL2 expression induced by UFAs.
• UFAs-induced CCL2 up-regulation is synergically mediated by NF-κB and STAT3.
• By blocking NF-κB and STAT3, 15d-PGJ2 inhibits the UFA-induced CCL2 expression.

Fatty acids (FAs) are massively released from peripancreatic fat during acute pancreatitis (AP) and they were shown, as a whole, to induce inflammatory response in pancreatic acini. We investigated the mechanisms triggered by the major saturated FAs (SFAs) and unsaturated FAs (UFAs) in modulating the expression of chemokine (C–C motif) ligand 2 (CCL2) in acinar cells. Pancreatic acini of control rats were treated with palmitic acid (PA) or stearic acid (SA), as SFAs, or oleic acid (OA) or linoleic acid (LA), as UFAs. By using specific inhibitors, the involvement of MAPKs (JNK, ERK, p38), JAK, NF-κB and STAT3 pathways was assessed. The role of PPARγ pathway was studied by using 15-Deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ2). CCL2 mRNA was analyzed by qRT-PCR. By western blot, phosphorylated forms of MAPKs and JAK as well as IκB-α were analyzed in cytoplasm and p65-NF-κB and phospho-STAT3 in nucleus. No effect was found in PA- or SA-treated acini. Conversely, in response to OA or LA, MAPKs and JAK acted as upstream signals, driving the CCL2 up-regulation transcriptionally mediated by the synergic action of NF-κB and STAT3. By blocking the activation of NF-κB and STAT3, 15d-PGJ2 totally inhibited the OA- and LA-induced CCL2 overexpression. We conclude that the most common UFAs, but not the SFAs, represented in peripancreatic fat and released during AP, are capable of up-regulating the acinar expression of CCL2, which depends on the activation of MAPK/JAK-mediated NF-κB and STAT3 pathways. By targeting both transcription factors, PPARγ agonists could be indicated as potential therapy in AP.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1852, Issue 12, December 2015, Pages 2671–2677
نویسندگان
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