Heat Stress Activates Interleukin-8 and the Antioxidant System via Nrf2 Pathways in Human Dental Pulp Cells
Department of Conservative Dentistry, The Institute of Oral Health Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Journal of endodontics
(Impact Factor: 3.38).
10/2009; 35(9):1222-8. DOI: 10.1016/j.joen.2009.06.005
This study tested whether heat stress (42 degrees C for 30 minutes) induces reactive oxygen species (ROS), proinflammatory cytokines, Nrf2 activation, and Nrf2 target genes such as antioxidant enzymes in human dental pulp (HDP) cells.
ROS was evaluated by using flow cytometry. Proteins and messenger RNA levels for cytokines and antioxidant genes were determined by using Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) analysis, respectively.
Heat stress induced the production of ROS and the increased expression of the interleukin (IL)-8 and IL-8 receptor genes. Exposure of cells to heat stress resulted in the nuclear translocation of Nrf2 and increased expression of Nrf2 target genes including heme oxygenase-1. Pretreatment with an exogenous antioxidant inhibited the heat-induced expression of IL-8 and Nrf2 target genes and Nrf2 translocation.
Collectively, these results show that heat-induced Nrf2 activation is the major regulatory pathway of cytoprotective gene expression against oxidative stress in HDP cells.
Available from: Krishna Kumar
- "Strong correlation has also been observed between activation of heat shock proteins and generation of CXC chemokines in response to heat shock in vitro as well as in vivo model systems; and activation of such a HS response during febrile range hyperthermia, inflammation, infections, and injury augments neutrophil delivery to the site of infection and injury (Nagarsekar et al. 2005). Heat stroke induces IL-8 production in blood leukocytes (Huisse et al. 2008) and activates expression of IL-8 and its receptor genes in human dental pulp cells (Chang et al. 2009). In the present study, higher IL-8 levels observed during parturition and in postpartum period in the hot–humid season confirms that IL-8 is indeed heat stress responsive in buffaloes. "
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ABSTRACT: The objective of this study was to elucidate the changes in circulating levels of plasma interleukin-8 (IL-8) during peripartum period in Murrah buffaloes (Bubalus bubalis). IL-8 was estimated in blood plasma of healthy peripartum Murrah buffaloes (n=6) on days ± 30, ± 15, ± 5, ± 3, ± 1 and 0 pre- and postpartum with respect to the day of parturition (day 0) in each of the two different seasons (hot-humid and spring). The mean microclimate Temperature-Humidity Index (THI) during spring season was significantly lower (p<0.01) than the corresponding THI in hot-humid season. In both the seasons, plasma IL-8 remained lower in prepartum period (≤ 46.56 ± 14.08 pg/ml during spring and ≤ 73.18 ± 18.56 pg/ml during hot-humid season) than in the postpartum period (≥ 51.41 ± 13.82 pg/ml during spring and ≥ 84.13 ± 16.97 pg/ml in hot humid season). During spring, the IL-8 levels were significantly higher (P<0.05) on days+5 and +15 postpartum in comparison to the IL-8 levels on days -30, -5, and -3 prepartum. During hot-humid season, IL-8 level was significantly higher (P<0.05) on day +30 as compared to the IL-8 levels on days -30 and -5 prepartum. The correlation between IL-8 and mean microclimate THI was significant (r=0.25, P<0.01). From the results, it is concluded that peripartum period in buffaloes is associated with an inflammatory response leading to significantly higher plasma IL-8 during parturition and postpartum period than in the pre-partum period.
Available from: John D Hayes
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ABSTRACT: Recognition and repair of cellular damage is crucial if organisms are to survive harmful environmental conditions. In mammals, the Keap1 protein orchestrates this response, but how it perceives adverse circumstances is not fully understood. Herein, we implicate NO, Zn(2+), and alkenals, endogenously occurring chemicals whose concentrations increase during stress, in this process. By combining molecular modeling with phylogenetic, chemical, and functional analyses, we show that Keap1 directly recognizes NO, Zn(2+), and alkenals through three distinct sensors. The C288 alkenal sensor is of ancient origin, having evolved in a common ancestor of bilaterans. The Zn(2+) sensor minimally comprises H225, C226, and C613. The most recent sensor, the NO sensor, emerged coincident with an expansion of the NOS gene family in vertebrates. It comprises a cluster of basic amino acids (H129, K131, R135, K150, and H154) that facilitate S-nitrosation of C151. Taken together, our data suggest that Keap1 is a specialized sensor that quantifies stress by monitoring the intracellular concentrations of NO, Zn(2+), and alkenals, which collectively serve as second messengers that may signify danger and/or damage.
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ABSTRACT: Fibroblast growth factor-2 (FGF-2) participates in both hematopoiesis and osteogenesis; however, the effects of FGF-2 on chemokines during odontoblastic differentiation have not been reported. This study investigated whether human dental pulp cells (HDPCs) treated with FGF-2 could express chemokines during differentiation into odontoblastic cells and sought to identify its underlying mechanism of action.
To analyze differentiation, we measured alkaline phosphatase (ALP) activity, calcified nodule formation by alizarin red staining, and marker RNA (mRNA) expression by reverse-transcriptase polymerase chain reaction (RT-PCR). Expression of chemokines, such as interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and MIP-3α, were evaluated by RT-PCR.
ALP activity, the mineralization, and mRNA expression for odontoblastic markers were enhanced by FGF-2 in HDPCs. FGF-2 also up-regulated the expression of IL-6, IL-8, MCP-1, MIP-1α, and MIP-3α mRNAs, which were attenuated by inhibitors of p38, ERK1/2 and p38 MAP kinases, protein kinase C, phosphoinositide-3 kinase, and NF-κB.
Taken together, these data suggest that FGF-2 plays a role not only as a differentiation inducing factor in the injury repair processes of pulpal tissue but also as a positive regulator of chemokine expression, which may help in tissue engineering and pulp regeneration using HDPCs. However, the fate of odontoblastic or osteoblastic differentiation, effective local delivery for FGF-2, interaction of chemotatic and odontogenic factors, and other limitations will need to be overcome before a major modality for the treatment of pulp disease.
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