Limits...
Activated pancreatic stellate cells can impair pancreatic islet function in mice.

Zang G, Sandberg M, Carlsson PO, Welsh N, Jansson L, Barbu A - Ups. J. Med. Sci. (2015)

Bottom Line: Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets.In islet transplants they were found mainly in the graft periphery.Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Cell Biology, Uppsala University , Uppsala , Sweden.

ABSTRACT

Background: Pancreatic or islet fibrosis is often associated with activated pancreatic stellate cells (PSCs). PSCs are considered not only to promote fibrosis, but also to be associated with glucose intolerance in some diseases. We therefore evaluated morphological and functional relationships between islets and PSCs in the normal mouse pancreas and transplanted islets.

Methods: Immunohistochemistry was used to map the presence of PSCs in the normal mouse pancreas and islets implanted under the renal capsule. We isolated and cultured mouse PSCs and characterized them morphologically by immunofluorescence staining. Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets.

Results: PSCs were scattered throughout the pancreas, with occasional cells within the islets, particularly in the islet capsule. In islet transplants they were found mainly in the graft periphery. Cultured PSCs became functionally activated and produced several cytokines. Throughout the culture period they linearly increased their production of interleukin-6 and mammalian keratinocyte-derived chemokine. PSC cytokine production was not affected by acute hyperglycemia. Syngeneic islets co-cultured with PSCs for 24-48 h increased their insulin release and lowered their insulin content. However, short-term insulin release in batch-type incubations was unaffected after 48 h of co-culture. Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days.

Conclusion: Activated PSCs may contribute to impaired islet endocrine function seen in exocrine pancreatitis and in islet fibrosis associated with some cases of type 2 diabetes.

No MeSH data available.


Related in: MedlinePlus

Medium release of interferon-γ (IFN-γ), interleukin-10 (IL-10), interleukin 12p70 (IL-12p70), interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and keratinocyte-derived chemokine (mKC) from PSCs after incubation for 24 h either alone or with added cytokines. The latter consisted of IL-6 (A: 10 ng/mL), IFN-γ (B: 1,000 U/mL), IL-1β (C: 50 U/mL), or IFN-γ + IL-1β (D: 1,000 U/mL + 50 U/mL). E: Cytokine concentrations in medium from mouse pancreatic stellate cells after different times of culture. Values are means ± SEM for 3–7 experiments. Note logarithmic scale in A–D. * P < 0.05, ** P < 0.01, and *** P < 0.001 compared with the corresponding control value. In E, values for mKC and IL-6 are higher (P < 0.01) at all times compared with their respective value at day 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4526872&req=5

Figure 6: Medium release of interferon-γ (IFN-γ), interleukin-10 (IL-10), interleukin 12p70 (IL-12p70), interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and keratinocyte-derived chemokine (mKC) from PSCs after incubation for 24 h either alone or with added cytokines. The latter consisted of IL-6 (A: 10 ng/mL), IFN-γ (B: 1,000 U/mL), IL-1β (C: 50 U/mL), or IFN-γ + IL-1β (D: 1,000 U/mL + 50 U/mL). E: Cytokine concentrations in medium from mouse pancreatic stellate cells after different times of culture. Values are means ± SEM for 3–7 experiments. Note logarithmic scale in A–D. * P < 0.05, ** P < 0.01, and *** P < 0.001 compared with the corresponding control value. In E, values for mKC and IL-6 are higher (P < 0.01) at all times compared with their respective value at day 3.

Mentions: PSCs produced high amounts of IL-1β, TNF-α, and mKC, and measurable quantities of IL-6 and IL-12p70 (Figure 6). PSCs were exposed to different cytokines for 24 h, and addition of IL-6 mainly increased the medium concentrations of IL-1β and TNF-α (Figure 6A), whilst addition of IFN-γ increased IL-6 medium concentrations (Figure 6B). Addition of IL-1β increased IL-6, IL-10, and mKC (Figure 6C), whereas the combined supplementation with IFN-γ and IL-1β increased concentrations of IL-6, IL-10, TNF-α , and mKC (Figure 6D) in the culture media.


Activated pancreatic stellate cells can impair pancreatic islet function in mice.

Zang G, Sandberg M, Carlsson PO, Welsh N, Jansson L, Barbu A - Ups. J. Med. Sci. (2015)

Medium release of interferon-γ (IFN-γ), interleukin-10 (IL-10), interleukin 12p70 (IL-12p70), interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and keratinocyte-derived chemokine (mKC) from PSCs after incubation for 24 h either alone or with added cytokines. The latter consisted of IL-6 (A: 10 ng/mL), IFN-γ (B: 1,000 U/mL), IL-1β (C: 50 U/mL), or IFN-γ + IL-1β (D: 1,000 U/mL + 50 U/mL). E: Cytokine concentrations in medium from mouse pancreatic stellate cells after different times of culture. Values are means ± SEM for 3–7 experiments. Note logarithmic scale in A–D. * P < 0.05, ** P < 0.01, and *** P < 0.001 compared with the corresponding control value. In E, values for mKC and IL-6 are higher (P < 0.01) at all times compared with their respective value at day 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526872&req=5

Figure 6: Medium release of interferon-γ (IFN-γ), interleukin-10 (IL-10), interleukin 12p70 (IL-12p70), interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and keratinocyte-derived chemokine (mKC) from PSCs after incubation for 24 h either alone or with added cytokines. The latter consisted of IL-6 (A: 10 ng/mL), IFN-γ (B: 1,000 U/mL), IL-1β (C: 50 U/mL), or IFN-γ + IL-1β (D: 1,000 U/mL + 50 U/mL). E: Cytokine concentrations in medium from mouse pancreatic stellate cells after different times of culture. Values are means ± SEM for 3–7 experiments. Note logarithmic scale in A–D. * P < 0.05, ** P < 0.01, and *** P < 0.001 compared with the corresponding control value. In E, values for mKC and IL-6 are higher (P < 0.01) at all times compared with their respective value at day 3.
Mentions: PSCs produced high amounts of IL-1β, TNF-α, and mKC, and measurable quantities of IL-6 and IL-12p70 (Figure 6). PSCs were exposed to different cytokines for 24 h, and addition of IL-6 mainly increased the medium concentrations of IL-1β and TNF-α (Figure 6A), whilst addition of IFN-γ increased IL-6 medium concentrations (Figure 6B). Addition of IL-1β increased IL-6, IL-10, and mKC (Figure 6C), whereas the combined supplementation with IFN-γ and IL-1β increased concentrations of IL-6, IL-10, TNF-α , and mKC (Figure 6D) in the culture media.

Bottom Line: Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets.In islet transplants they were found mainly in the graft periphery.Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Cell Biology, Uppsala University , Uppsala , Sweden.

ABSTRACT

Background: Pancreatic or islet fibrosis is often associated with activated pancreatic stellate cells (PSCs). PSCs are considered not only to promote fibrosis, but also to be associated with glucose intolerance in some diseases. We therefore evaluated morphological and functional relationships between islets and PSCs in the normal mouse pancreas and transplanted islets.

Methods: Immunohistochemistry was used to map the presence of PSCs in the normal mouse pancreas and islets implanted under the renal capsule. We isolated and cultured mouse PSCs and characterized them morphologically by immunofluorescence staining. Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets.

Results: PSCs were scattered throughout the pancreas, with occasional cells within the islets, particularly in the islet capsule. In islet transplants they were found mainly in the graft periphery. Cultured PSCs became functionally activated and produced several cytokines. Throughout the culture period they linearly increased their production of interleukin-6 and mammalian keratinocyte-derived chemokine. PSC cytokine production was not affected by acute hyperglycemia. Syngeneic islets co-cultured with PSCs for 24-48 h increased their insulin release and lowered their insulin content. However, short-term insulin release in batch-type incubations was unaffected after 48 h of co-culture. Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days.

Conclusion: Activated PSCs may contribute to impaired islet endocrine function seen in exocrine pancreatitis and in islet fibrosis associated with some cases of type 2 diabetes.

No MeSH data available.


Related in: MedlinePlus