Activated cholangiocytes release macrophage-polarizing extracellular vesicles bearing the DAMP S100A11

In mouse models of biliary tract diseases, macrophages are recruited to the periductal milieu and promote injury and cholestasis. Although cell necrosis with release of biomolecules termed damage-associated molecular patterns (DAMPs) promotes recruitment and activation of macrophages, necrosis was not observed in these studies. Because extracellular vesicles (EVs) are important in cell-to-cell communication, we postulated that activated cholangiocytes may release EVs containing DAMPs as cargo. Both the human (NHC) and mouse cholangiocyte (603B) cell lines display constitutive activation with mRNA expression of chemokines. Proteomic analysis revealed that EVs from both cell lines contained the DAMP S100A11, a ligand for the receptor for advanced glycation end products (RAGE). Bone marrow-derived macrophages (BMDM) incubated with EVs derived from the mouse 603B cell line increased mRNA expression of proinflammatory cytokines. Genetic or pharmacologic inhibition of RAGE reduced BMDM expression of proinflammatory cytokines treated with EVs. RAGE signaling resulted in activation of the canonical NF-κB pathway, and consistently, proinflammatory cytokine expression was blunted by the IKKα/β inhibitor TPCA-1 in BMDM incubated with EVs. We also demonstrated that primary mouse cholangiocyte-derived organoids express chemokines indicating cholangiocyte activation, release EVs containing S100A11, and stimulate proinflammatory cytokine expression in BMDM by a RAGE-dependent pathway. In conclusion, these observations identify a non-cell death mechanism for cellular release of DAMPs by activated cholangiocytes, namely by releasing DAMPs as EV cargo. These data also suggest RAGE inhibitors may be salutary in macrophage-associated inflammatory diseases of the bile ducts.

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Inhibition of Proinflammatory Cytokines in Cutibacterium acnes-Induced Inflammation in HaCaT Cells by Using Buddleja davidii Aqueous Extract

International Journal of Inflammation ◽

10.1155/2020/8063289 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Anh Thu Nguyen ◽

Ki-young Kim

Keyword(s):

Proinflammatory Cytokines ◽

Proinflammatory Cytokine ◽

Treatment Options ◽

Mapk Signaling ◽

Cytokine Expression ◽

Proinflammatory Cytokine Expression ◽

Cutibacterium Acnes ◽

Anti Inflammatory ◽

New Treatment ◽

Hacat Keratinocyte

Acne is an inflammatory skin disorder; although some anti-inflammatory medicines for treating acne are available in a market, they have considerable side effects; therefore, new treatment options are needed. In the present study, among the 16 aqueous extracts of plants collected from Jeju Island in Korea which are used to test anti-inflammatory activity, B. davidii showed the strong decline of the proinflammatory cytokine expression against the inflammatory process caused by C. acnes in Human HaCaT keratinocyte cells. B. davidii downregulated the expression of 57% of COX-2, 41% of iNOS, and proinflammatory cytokines 29% of TNF-α, 32% of IL-1β, 21% of IL-6, and 35% of IL-8. Furthermore, B. davidii inhibited NF-κB and MAPK signaling cascades in keratinocytes that activated by toll-like receptor 2 (TLR-2) in response to C. acnes. Given those results, B. davidii is a potential agent to reduce the proinflammatory cytokine expression against C. acnes-induced inflammation and might provide an alternative to the current medications.

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Differential Regulation of Proinflammatory Cytokine Expression by Mitogen-Activated Protein Kinases in Macrophages in Response to Intestinal Parasite Infection

Infection and Immunity ◽

10.1128/iai.02279-14 ◽

2014 ◽

Vol 82 (11) ◽

pp. 4789-4801 ◽

Cited By ~ 26

Author(s):

Mei Xing Lim ◽

Chin Wen Png ◽

Crispina Yan Bing Tay ◽

Joshua Ding Wei Teo ◽

Huipeng Jiao ◽

...

Keyword(s):

Protein Expression ◽

Proinflammatory Cytokines ◽

Proinflammatory Cytokine ◽

Map Kinases ◽

Cytokine Expression ◽

Content Type ◽

Erk Activation ◽

Proinflammatory Cytokine Expression ◽

Tnf Α ◽

Mitogen Activated Protein

ABSTRACTBlastocystisis a common enteric protistan parasite that can cause acute, as well as chronic, infection and is associated with irritable bowel syndrome (IBS). However, the pathogenic status ofBlastocystisinfection remains unclear. In this study, we found thatBlastocystisantigens induced abundant expression of proinflammatory cytokines, including interleukin 1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α), in mouse intestinal explants, in mouse colitis colon, and in macrophages. Further investigation utilizing RAW264.7 murine macrophages showed thatBlastocystistreatment in RAW264.7 macrophages induced the activation of ERK, JNK, and p38, the three major groups of mammalian mitogen-activated protein (MAP) kinases that play essential roles in the expression of proinflammatory cytokines. ERK inhibition in macrophages significantly suppressed both mRNA and protein expression of IL-6 and TNF-α and mRNA expression of IL-1β. On the other hand, JNK inhibition resulted in reductions in both c-Jun and ERK activation and significant suppression of all three proinflammatory cytokines at both the mRNA and protein levels. Inhibition of p38 suppressed only IL-6 protein expression with no effect on the expression of IL-1β and TNF-α. Furthermore, we found that serine proteases produced byBlastocystisplay an important role in the induction of ERK activation and proinflammatory cytokine expression by macrophages. Our study thus demonstrated for the first time thatBlastocystiscould induce the expression of various proinflammatory cytokines via the activation of MAP kinases and that infection withBlastocystismay contribute to the pathogenesis of inflammatory intestinal diseases through the activation of inflammatory pathways in host immune cells, such as macrophages.

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Proinflammatory cytokine expression by Theileria annulata infected cell lines correlates with the pathology they cause in vivo

Vaccine ◽

10.1016/s0264-410x(00)00529-6 ◽

2001 ◽

Vol 19 (20-22) ◽

pp. 2932-2944 ◽

Cited By ~ 32

Author(s):

Simon P Graham ◽

David J Brown ◽

Zati Vatansever ◽

David Waddington ◽

Louise H Taylor ◽

...

Keyword(s):

Infected Cell ◽

Cell Lines ◽

Proinflammatory Cytokine ◽

Cytokine Expression ◽

Theileria Annulata ◽

Proinflammatory Cytokine Expression

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SUN-P093: Effects of EPA, DHA and Oxaliplatin on Proinflammatory Cytokine Expression in two Oesophageal Adenocarcinoma Cell Lines

Clinical Nutrition ◽

10.1016/s0261-5614(16)30436-8 ◽

2016 ◽

Vol 35 ◽

pp. S78-S79

Author(s):

A.M. Eltweri ◽

L.M. Howells ◽

A.L. Thomas ◽

A.R. Dennison ◽

D.J. Bowrey

Keyword(s):

Cell Lines ◽

Proinflammatory Cytokine ◽

Cytokine Expression ◽

Oesophageal Adenocarcinoma ◽

Adenocarcinoma Cell ◽

Proinflammatory Cytokine Expression

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The Effect of Exercise and Nutritional Supplementation on Proinflammatory Cytokine Expression in Young Racehorses During Training

Journal of Equine Veterinary Science ◽

10.1016/j.jevs.2012.03.017 ◽

2012 ◽

Vol 32 (12) ◽

pp. 805-815 ◽

Cited By ~ 22

Author(s):

David W. Horohov ◽

Stephen T. Sinatra ◽

Raj K. Chopra ◽

Stanley Jankowitz ◽

Alejandra Betancourt ◽

...

Keyword(s):

Proinflammatory Cytokine ◽

Cytokine Expression ◽

Nutritional Supplementation ◽

Proinflammatory Cytokine Expression

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Changes in peritoneal myeloid populations and their proinflammatory cytokine expression during infection withListeria monocytogenesare altered in the absence of γ/δ T cells

Journal of Leukocyte Biology ◽

10.1189/jlb.1103574 ◽

2004 ◽

Vol 76 (1) ◽

pp. 104-115 ◽

Cited By ~ 20

Author(s):

Marianne J. Skeen ◽

Molly M. Freeman ◽

H. Kirk Ziegler

Keyword(s):

T Cells ◽

Proinflammatory Cytokine ◽

Cytokine Expression ◽

Proinflammatory Cytokine Expression

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Diet-Derived Advanced Glycation End Products (dAGEs) Induce Proinflammatory Cytokine Expression in Cardiac and Renal Tissues of Experimental Mice: Protective Effect of Curcumin

Cardiovascular Toxicology ◽

10.1007/s12012-021-09697-4 ◽

2021 ◽

Author(s):

Boopathi Sowndhar Rajan ◽

Kalaiselvi Krishnan ◽

Elangovan Vellaichamy

Keyword(s):

Protective Effect ◽

Advanced Glycation End Products ◽

Proinflammatory Cytokine ◽

Cytokine Expression ◽

Advanced Glycation ◽

Proinflammatory Cytokine Expression ◽

Glycation End Products ◽

End Products

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Multiplexed Profiling of Single-cell Extracellular Vesicles Secretion

10.1101/459438 ◽

2018 ◽

Author(s):

Yahui Ji ◽

Dongyuan Qi ◽

Linmei Li ◽

Haoran Su ◽

Xiaojie Li ◽

...

Keyword(s):

Single Cell ◽

Cell Lines ◽

Extracellular Vesicles ◽

Single Cells ◽

Cell Communication ◽

Deep Understanding ◽

Surface Markers ◽

Cell Heterogeneity ◽

Health And Disease ◽

Cytokines Secretion

AbstractExtracellular vesicles (EVs) are important intercellular mediators regulating health and disease. Conventional EVs surface marker profiling, which was based on population measurements, masked the cell-to-cell heterogeneity in the quantity and phenotypes of EVs secretion. Herein, by using spatially patterned antibodies barcode, we realized multiplexed profiling of single-cell EVs secretion from more than 1000 single cells simultaneously. Applying this platform to profile human oral squamous cell carcinoma (OSCC) cell lines led to deep understanding of previously undifferentiated single cell heterogeneity underlying EVs secretion. Notably, we observed the decrement of certain EV phenotypes (e.g. CD63+EVs) were associated with the invasive feature of both OSCC cell lines and primary OSCC cells. We also realized multiplexed detection of EVs secretion and cytokines secretion simultaneously from the same single cells to investigate multidimensional spectrum of intercellular communications, from which we resolved three functional subgroups with distinct secretion profiles by visualized clustering. In particular, we found EVs secretion and cytokines secretion were generally dominated by different cell subgroups. The technology introduced here enables comprehensive evaluation of EVs secretion heterogeneity at single cell level, which may become an indispensable tool to complement current single cell analysis and EV research.SignificanceExtracellular vesicles (EVs) are cell derived nano-sized particles medicating cell-cell communication and transferring biology information molecules like nucleic acids to regulate human health and disease. Conventional methods for EV surface markers profiling can’t tell the differences in the quantity and phenotypes of EVs secretion between cells. To address this need, we developed a platform for profiling an array of surface markers on EVs from large numbers of single cells, enabling more comprehensive monitoring of cellular communications. Single cell EVs secretion assay led to previously unobserved cell heterogeneity underlying EVs secretion, which might open up new avenues for studying cell communication and cell microenvironment in both basic and clinical research.

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