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

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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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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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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