βig-h3-structured Collagen Alters Macrophage Phenotype and Function in Pancreatic Cancer

Background: The Toll-like receptor (TLR) family is involved in the recognition of and response to microbial infections. These receptors are expressed in leukocytes. TLR stimulation induces the production of proinflammatory cytokines and chemokines. Given that human lung macrophages (LMs) constitute the first line of defense against inhaled pathogens, the objective of this study was to investigate the expression and function of TLR subtypes in this cell population. Methods: Human primary LMs were obtained from patients undergoing surgical resection. The RNA and protein expression levels of TLRs, chemokines, and cytokines were assessed after incubation with subtype-selective agonists. Results: In human LMs, the TLR expression level varied from one subtype to another. Stimulation with subtype-selective agonists induced an intense, concentration- and time-dependent increase in the production of chemokines and cytokines. TLR4 stimulation induced the strongest effect, whereas TLR9 stimulation induced a much weaker response. Conclusions: The stimulation of TLRs in human LMs induces intense cytokine and chemokine production, a characteristic of the proinflammatory M1 macrophage phenotype.

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Design and Function of Engineered Protein Nanocages as a Drug Delivery System for Targeting Pancreatic Cancer Cells via Neuropilin-1

Molecular Pharmaceutics ◽

10.1021/mp5007129 ◽

2015 ◽

Vol 12 (5) ◽

pp. 1422-1430 ◽

Cited By ~ 23

Author(s):

Masaharu Murata ◽

Sayoko Narahara ◽

Takahito Kawano ◽

Nobuhito Hamano ◽

Jing Shu Piao ◽

...

Keyword(s):

Drug Delivery ◽

Pancreatic Cancer ◽

Cancer Cells ◽

Drug Delivery System ◽

Delivery System ◽

Pancreatic Cancer Cells ◽

Neuropilin 1 ◽

And Function

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Focal adhesion kinase signaling and function in pancreatic cancer

Frontiers in Bioscience ◽

10.2741/e283 ◽

2011 ◽

Vol E3 (2) ◽

pp. 750-756 ◽

Cited By ~ 3

Author(s):

Steven N Hochwald

Keyword(s):

Pancreatic Cancer ◽

Focal Adhesion Kinase ◽

Focal Adhesion ◽

Kinase Signaling ◽

And Function ◽

Focal Adhesion Kinase Signaling

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Serum Amyloid A1 Induces Classically Activated Macrophages: A Role for Enhanced Fibril Formation

Frontiers in Immunology ◽

10.3389/fimmu.2021.691155 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ann-Kathrin Gaiser ◽

Shanna Bauer ◽

Stephanie Ruez ◽

Karlheinz Holzmann ◽

Marcus Fändrich ◽

...

Keyword(s):

Amyloid Fibrils ◽

Intervention Strategy ◽

Serum Amyloid ◽

Macrophage Phenotype ◽

Aa Amyloidosis ◽

Inflammatory Conditions ◽

Serum Amyloid A1 ◽

And Function

AA amyloidosis belongs to the group of amyloid diseases which can follow chronic inflammatory conditions of various origin. The disease is characterized by the deposition of insoluble amyloid fibrils formed by serum amyloid A1 (SAA1) leading eventually to organ failure. Macrophages are intimately involved in the fibrillogenesis as well as in the clearance of amyloid fibrils. In vivo, macrophages may occur as classically (M1) or alternatively activated (M2) macrophages. We investigate here how SAA1 might affect the macrophage phenotype and function. Gene microarray analysis revealed upregulation of 64 M1-associated genes by SAA1. M1-like polarization was further confirmed by the expression of the M1-marker MARCO, activation of the NF-κB transcription factor, and secretion of the M1-cytokines TNF-α, IL-6, and MCP-1. Additionally, we demonstrate here that M1-polarized macrophages exhibit enhanced fibrillogenic activity towards SAA1. Based on our data, we propose reconsideration of the currently used cellular amyloidosis models towards an in vitro model employing M1-polarized macrophages. Furthermore, the data suggest macrophage repolarization as potential intervention strategy in AA amyloidosis.

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Abstract B39: Regulation and function of IL-1b in immune modulation of pancreatic cancer

10.1158/2326-6074.tumimm18-b39 ◽

2020 ◽

Author(s):

Shipra Das ◽

Sandra Vogt ◽

Christina Hadju ◽

Dafna Bar-Sagi

Keyword(s):

Pancreatic Cancer ◽

Immune Modulation ◽

And Function

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Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer

Cancers ◽

10.3390/cancers12123631 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3631

Author(s):

Krystal Villalobos-Ayala ◽

Ivannie Ortiz Rivera ◽

Ciara Alvarez ◽

Kazim Husain ◽

DeVon DeLoach ◽

...

Keyword(s):

Pancreatic Cancer ◽

Immune Responses ◽

Suppressor Cells ◽

Myeloid Cell ◽

Tumor Burden ◽

Sh2 Domain ◽

Src Homology 2 ◽

Src Homology ◽

And Function ◽

Deficient Mice

Pancreatic cancer (PC) has an extremely poor prognosis due to the expansion of immunosuppressive myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) in the inflammatory tumor microenvironment (TME), which halts the recruitment of effector immune cells and renders immunotherapy ineffective. Thus, the identification of new molecular targets that can modulate the immunosuppressive TME is warranted for PC intervention. Src Homology-2 (SH2) domain-containing Inositol 5′-Phosphatase-1 (SHIP-1) is a lipid signaling protein and a regulator of myeloid cell development and function. Herein, we used the bioflavonoid apigenin (API) to reduce inflammation in different PC models. Wild type mice harboring heterotopic or orthotopic PC were treated with API, which induced SHIP-1 expression, reduced inflammatory tumor-derived factors (TDF), increased the proportion of tumoricidal macrophages and enhanced anti-tumor immune responses, resulting in a reduction in tumor burden compared to vehicle-treated PC mice. In contrast, SHIP-1-deficient mice exhibited an increased tumor burden and displayed augmented proportions of pro-tumor macrophages. These results provide further support for the importance of SHIP-1 expression in promoting pro-tumor macrophage development in the pancreatic TME. Our findings suggest that agents augmenting SHIP-1 expression may provide novel therapeutic options for the treatment of PC.

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