scholarly journals Induction of proinflammatory cytokine production in intervertebral disc cells by macrophage-like THP-1 cells requires mitogen-activated protein kinase activity

2016 ◽  
Vol 24 (1) ◽  
pp. 167-175 ◽  
Author(s):  
Jung Jae Park ◽  
Hong Joo Moon ◽  
Jin Hyun Park ◽  
Taek Hyun Kwon ◽  
Youn-Kwan Park ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Intervertebral Disc ◽  
Proinflammatory Cytokines ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Protein Kinase Activity ◽  
Inflammatory Reactions ◽  
Selective Blockade ◽  
Tnf Α ◽  
Mitogen Activated Protein

OBJECT To determine the role played by mitogen-activated protein kinase (MAPK) signaling in the interactions between macrophages and intervertebral disc (IVD) cells, it was hypothesized that MAPK inhibition would modulate the production of the proinflammatory cytokines associated with inflammatory reaction in IVD cells. METHODS Human annulus fibrosus (AF) and nucleus pulposus (NP) cells were cocultured with phorbol myristate acetate-stimulated macrophage-like THP-1 cells, with and without SB202190 (a p38-α and -β inhibitor), SP600125 (a c-Jun N-terminal kinase [JNK] inhibitor), and PD98059 (an extracellular signal-regulated kinase [ERK] 1/2 inhibitor). The cytokines in conditioned media from cocultured and macrophage-exposed (nemotic) cells were assayed using enzyme-linked immunosorbent assays (ELISAs). RESULTS Interleukin (IL)-6 and IL-8 were secreted in greater quantities by the cocultured cells compared with naive IVD cells and macrophages (MΦ) cultured alone. The tumor necrosis factor (TNF)- α and IL-6 levels produced by the NP cells cocultured with MΦs (NP-MΦ) were significantly lower than those produced by AF cells cocultured with MΦs (AF-MΦ). SB202190 dose-dependently suppressed IL-6 secretion by AF-MΦ and NP-MΦ cocultures, and 10 μM SB202190 significantly decreased IL-6 and IL-8 production in nemotic AF and NP pellets. SP600125 at 10 μM significantly suppressed the production of TNF α IL-6. and IL-8 in AF-MΦ and NP-MΦ cocultures and significantly suppressed IL-1β production in the NP-MΦ coculture. Administration of 10 μM PD98059 significantly decreased IL-6 levels in the AF-MΦ coculture, and decreased the levels of TNF α and IL-8 in both the AF-MΦ and NP-MΦ cocultures. CONCLUSIONS The present study shows that inhibitors of p38 MAPK effectively controlled IL-6 production during inflammatory reactions and that JNK and ERK1/2 inhibitors successfully suppressed the production of major proinflammatory cytokines during interactions between macrophages and IVD cells. Therefore, selective blockade of these signals may serve as a therapeutic approach to symptomatic IVD degeneration.

scholarly journals Chicken avian β-defensin 8 modulates immune response via the mitogen-activated protein kinase signaling pathways in a chicken macrophage cell line

2019 ◽  
Author(s):  
Yeojin Hong ◽  
Thu Thao Pham ◽  
Jiae Lee ◽  
Hyun S. Lillehoj ◽  
Yeong Ho Hong
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Proinflammatory Cytokines ◽  
Interferon Γ ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Macrophage Cell ◽  
Mitogen Activated Protein ◽  
Chicken Macrophage

Abstract Background Defensins are antimicrobial peptides composed of three conserved disulfide bridges, a β-sheet, and both hydrophobic and cationic amino acids. In this study, we aimed to demonstrate the immunomodulation role of avian β-defensin 8 (AvBD8) in a chicken macrophage cell line.Results Chicken AvBD8 stimulated the expression of proinflammatory cytokines (interleukin (IL)-1β, interferon-γ, and IL-12p40) and chemokines (CCL4, CXCL13, and CCL20) in macrophages. Furthermore, by western blotting and immunocytochemistry, we confirmed that AvBD8 activated the mitogen-activated protein kinase (MAPK) signaling pathway via extracellular regulated kinases 1/2 (ERK1/2) and p38 signaling molecules.Conclusion Overall, AvBD8 plays a crucial role in host defense as not only an antimicrobial peptide, but also an immunomodulator by activating the MAPK signaling pathway and inducing the expression of proinflammatory cytokines and chemokines.

Extracellular signal–regulated protein kinase signaling pathway negatively regulates the phenotypic and functional maturation of monocyte-derived human dendritic cells

Blood ◽  
2001 ◽  
Vol 98 (7) ◽  
pp. 2175-2182 ◽  
Author(s):  
Amaya Puig-Kröger ◽  
Miguel Relloso ◽  
Oskar Fernández-Capetillo ◽  
Ana Zubiaga ◽  
Augusto Silva ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Protein Kinase ◽  
Intracellular Signaling ◽  
Mannose Receptor ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Functional Maturation ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Mitogen Activated Protein

Dendritic cells (DC) are highly specialized antigen-presenting cells that on activation by inflammatory stimuli (eg, tumor necrosis factor α [TNF-α] and interleukin-1β [IL-1β]) or infectious agents (eg, lipopolysaccharide [LPS]), mature and migrate into lymphoid organs. During maturation, DC acquire the capacity to prime and polarize resting naive T lymphocytes. Maturation of monocyte-derived DC (MDDC) is inhibited by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. This study found that in the presence of the mitogen-activated protein kinase kinase 1–extracellular signal-regulated kinase (ERK) inhibitors PD98059 or U0126, TNF-α– and LPS-induced phenotypic and functional maturation is enhanced. ERK pathway inhibitors increased expression of major histocompatibility complex and costimulatory molecules; loss of mannose-receptor–mediated endocytic activity; nuclear factor-κB DNA-binding activity; release of IL-12 p40; and allogeneic T-cell proliferation induced by LPS or TNF-α. Moreover, PD98059 and U0126 enhanced LPS-triggered production of IL-12 p70. In agreement with the effect of ERK inhibitors, maturation of MDDC was delayed in the presence of serum, an effect that was reversed by U0126. These results indicate that the ERK and p38 MAPK signaling pathways differentially regulate maturation of MDDC and suggest that their relative levels of activation might modulate the initial commitment of naive T-helper (Th) cells toward Th1 or Th2 subsets. The findings also suggest that maturation of MDDC might be pharmacologically modified by altering the relative levels of activation of both intracellular signaling routes.

scholarly journals Chicken avian β-defensin 8 modulates immune response via the mitogen-activated protein kinase signaling pathways in a chicken macrophage cell line

2020 ◽  
Author(s):  
Yeojin Hong ◽  
Thu Thao Pham ◽  
Jiae Lee ◽  
Hyun S. Lillehoj ◽  
Yeong Ho Hong
Keyword(s):  
Protein Kinase ◽  
Cell Line ◽  
Signaling Pathway ◽  
Proinflammatory Cytokines ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Mitogen Activated Protein ◽  
Chicken Macrophage

Abstract Background: Defensins are antimicrobial peptides composed of three conserved disulfide bridges, a β-sheet, and both hydrophobic and cationic amino acids. In this study, we aimed to demonstrate the immunomodulation role of avian β-defensin 8 (AvBD8) in a chicken macrophage cell line. Results: Chicken AvBD8 stimulated the expression of proinflammatory cytokines (interleukin (IL)-1β, interferon-γ, and IL-12p40) and chemokines (CCL4, CXCL13, and CCL20) in macrophages. Furthermore, by western blotting and immunocytochemistry, we confirmed that AvBD8 activated the mitogen-activated protein kinase (MAPK) signaling pathway via extracellular regulated kinases 1/2 (ERK1/2) and p38 signaling molecules. Conclusion: Overall, AvBD8 regulates host immune system as not only an antimicrobial peptide, but also an immunomodulator by activating the MAPK signaling pathway and inducing the expression of proinflammatory cytokines and chemokines.

scholarly journals Topical Spilanthol Inhibits MAPK Signaling and Ameliorates Allergic Inflammation in DNCB-Induced Atopic Dermatitis in Mice

2019 ◽  
Vol 20 (10) ◽  
pp. 2490 ◽  
Author(s):  
Wen-Chung Huang ◽  
Chun-Hsun Huang ◽  
Sindy Hu ◽  
Hui-Ling Peng ◽  
Shu-Ju Wu
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cells ◽  
Protein Kinase ◽  
Allergic Inflammation ◽  
Skin Lesions ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Pathways ◽  
Mitogen Activated Protein ◽  
Cox 2

Atopic dermatitis (AD) is a recurrent allergic skin disease caused by genetic and environmental factors. Patients with AD may experience immune imbalance, increased levels of mast cells, immunoglobulin (Ig) E and pro-inflammatory factors (Cyclooxygenase, COX-2 and inducible NO synthase, iNOS). While spilanthol (SP) has anti-inflammatory and analgesic activities, its effect on AD remains to be explored. To develop a new means of SP, inflammation-related symptoms of AD were alleviated, and 2,4-dinitrochlorobenzene (DNCB) was used to induce AD-like skin lesions in BALB/c mice. Histopathological analysis was used to examine mast cells and eosinophils infiltration in AD-like skin lesions. The levels of IgE, IgG1 and IgG2a were measured by enzyme-linked immunosorbent assay (ELISA) kits. Western blot was used for analysis of the mitogen-activated protein kinase (MAPK) pathways and COX-2 and iNOS protein expression. Topical SP treatment reduced serum IgE and IgG2a levels and suppressed COX-2 and iNOS expression via blocked mitogen-activated protein kinase (MAPK) pathways in DNCB-induced AD-like lesions. Histopathological examination revealed that SP reduced epidermal thickness and collagen accumulation and inhibited mast cells and eosinophils infiltration into the AD-like lesions skin. These results indicate that SP may protect against AD skin lesions through inhibited MAPK signaling pathways and may diminish the infiltration of inflammatory cells to block allergic inflammation.

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