Regulation of Chemokine Production via Oxidative Pathway in HeLa Cells

Kina, Shinichiro; Nakasone, Toshiyuki; Takemoto, Hiroyuki; Matayoshi, Akira; Makishi, Shoko; Sunagawa, Nao; Liang, Feixin; Phonaphonh, Thongsavanh; Sunakawa, Hajime

doi:10.1155/2009/183760

Cited by 10 publications

(9 citation statements)

References 25 publications

(37 reference statements)

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“…3C). (16,38). Notably, we noticed that the DN-duox1 recruitment curve presented a kinetics very similar to that obtained for cxcl8-l2 morphants (10) (Fig.…”

Section: Cxcl8-l2 and Ltb4 Are Involved In Early Neutrophil Recruitmentsupporting

confidence: 82%

Duox1-Derived H2O2 Modulates Cxcl8 Expression and Neutrophil Recruitment via JNK/c-JUN/AP-1 Signaling and Chromatin Modifications

Oliveira

Boudinot²,

Calado

et al. 2015

The Journal of Immunology

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DUOX1-derived hydrogen peroxide (H2O2) and CXCL8 are two key neutrophil chemoattractants. H2O2 is critical at the early phase, whereas CXCL8 plays a key role in the late phases of recruitment, but the crosstalks between the two phases in vivo remain unknown. In this study using zebrafish, we report that H2O2 also contributes to neutrophil recruitment to injuries at the late phase as it induces Cxcl8 expression in vivo through a JNK/c-JUN/AP-1 signaling pathway. However, Erk and NF-κB signaling were not involved in this crosstalk. Strikingly, H2O2 also promotes cxcl8 expression through modulation of histone 3 lysine 4 trimethylation, histone 3 lysine 9 acetylation, and histone 3 lysine 9 trimethylation levels at its promoter. These results explain how early H2O2 signal regulates neutrophil recruitment at all phases, directly via Lyn oxidation or indirectly by modulating cxcl8 gene expression, via the activation of redox-sensitive signaling pathways, and further point out H2O2/DUOX1 as a key drug target for anti-inflammatory therapies.

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“…3C). (16,38). Notably, we noticed that the DN-duox1 recruitment curve presented a kinetics very similar to that obtained for cxcl8-l2 morphants (10) (Fig.…”

Section: Cxcl8-l2 and Ltb4 Are Involved In Early Neutrophil Recruitmentsupporting

confidence: 82%

Duox1-Derived H2O2 Modulates Cxcl8 Expression and Neutrophil Recruitment via JNK/c-JUN/AP-1 Signaling and Chromatin Modifications

Oliveira

Boudinot²,

Calado

et al. 2015

The Journal of Immunology

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“…The link between neutrophils and pancreatic production of MIP-2 is not known but may be related to proinflammatory compounds secreted from activated leukocytes, which in turn, may activate tissue-resident cells in the pancreas. For example, neutrophils can generate large quantities of ROS, which have been shown to induce chemokine synthesis [41,42].…”

Section: Discussionmentioning

confidence: 99%

Role of neutrophils in the activation of trypsinogen in severe acute pancreatitis

Abdulla

Awla

Thorlacius

et al. 2011

Journal of Leukocyte Biology

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The relationship between inflammation and proteolytic activation in pancreatitis is an unresolved issue in pancreatology. The purpose of this study was to define the influence of neutrophils on trypsinogen activation in severe AP. Pancreatitis was induced by infusion of taurocholate into the pancreatic duct in C57BL/6 mice. For neutrophil depletion, an anti-Gr-1 antibody was administered before pancreatitis induction. Administration of the anti-Gr-1 antibody reduced circulating neutrophils by 97%. Pancreatic TAP and serum amylase levels increased 2 h and 24 h after induction of pancreatitis. Neutrophil depletion reduced pancreatic TAP and serum amylase levels at 24 h but not at 2 h after pancreatitis induction. Pancreatic MPO and infiltration of neutrophils, as well as MIP-2 levels, were increased 24 h after taurocholate infusion. Two hours after taurocholate administration, no significant pancreatic infiltration of neutrophils was observed. Injection of the anti-Gr-1 antibody abolished MPO activity, neutrophil accumulation, and MIP-2 levels, as well as acinar cell necrosis, hemorrhage, and edema in the pancreas at 24 h. Moreover, taurocholate-provoked tissue damage and MPO activity in the lung were normalized by neutrophil depletion. Intravital fluorescence microscopy revealed a 97% reduction of leukocytes in the pancreatic microcirculation after administration of the anti-Gr-1 antibody. Our data demonstrate that initial trypsinogen activation is independent of neutrophils, whereas later activation is dependent on neutrophils in the pancreas. Neutrophils are critical in mediating pancreatic and lung tissue damage in severe AP.

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“…Additionally, we showed that IL8 and MCP1 gene and protein expression increased well before apoptosis occurred, as early as 1–2 hours after HRPE cell co-culture with unstimulated monocytes, and correlated with increases in FPF levels and reductions in ΔΨm (Figs 3–5). One possible explanation for prompt HRPE chemokine induction is the high levels of ROM induced by monocyte-binding to mouse or human RPE cells (Yoshida et al, 2003; Yang et al, 2009), because oxidative stressors have been shown to induce IL8 and MCP1 production in other cell types (Zeng et al, 2003; Kina et al, 2009). Interestingly, production of HRPE MCP1 was significantly inhibited by NAC while that of IL8 was not (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…ROM have also been shown to mediate production of pro-inflammatory chemokines, interleukin-8 ( IL8 ) and monocyte chemotactic factor-1 ( MCP1 ), also known as CC motif ligand 2 ( CCL2 ) (Zeng et al, 2003; Kina et al, 2009), which modulate ocular inflammatory responses, including leukocyte chemotaxis and activation within the eye (Yoshida et al, 2001a). IL8 and MCP1 are the principal chemokines secreted by HRPE cells and have been implicated in a number of retinal diseases (Yoshida et al, 2001a; Bian et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Retinal flavoprotein fluorescence correlates with mitochondrial stress, apoptosis, and chemokine expression

Field

Yang

Bian

et al. 2011

Experimental Eye Research

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Oxidative stress and mitochondrial dysfunction occur before apoptosis in many retinal diseases. Under these conditions, a larger fraction of flavoproteins become oxidized and, when excited by blue-light, emit green flavoprotein fluorescence (FPF). In this study, we evaluated the utility of FPF as an early indicator of mitochondrial stress, pre-apoptotic cellular instability, and apoptosis of human retinal pigment epithelial (HRPE) cells subjected to hydrogen peroxide (H2O2) or monocytes (unstimulated or interferon-γ-stimulated) in vitro and of freshly isolated pieces of human and rat neural retina subjected to H2O2 ex vivo. Increased FPF of HRPE cells exposed to H2O2 correlated with reduced mitochondrial membrane potential (ΔΨm) and increased apoptosis in a time- and dose-dependent manner. HRPE cells co-cultured with monocytes had increased FPF that correlated in a time-dependent manner with reduced ΔΨm, increased apoptosis, and early expression of pro-inflammatory chemokines, interleukin-8 (IL8) and monocyte chemotactic factor-1 (MCP1), which are known to be induced by oxidative stress. Increased FPF, reduced ΔΨm, and upregulation of IL8 and MCP1 occurred as early as 1–2 hours after exposure to stressors, while apoptosis did not occur in HRPE cells until later time points. The antioxidant, N-aceytl-cysteine (NAC), inhibited increased FPF and apoptosis of HRPE cells subjected to H2O2. Increased FPF of human and rat neural retina also correlated with increased apoptosis. This study suggests that FPF is a useful measure of mitochondrial function in retinal cells and tissues and can detect early mitochondrial dysfunction that may precede apoptosis.

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Regulation of Chemokine Production via Oxidative Pathway in HeLa Cells

Cited by 10 publications

References 25 publications

Duox1-Derived H2O2 Modulates Cxcl8 Expression and Neutrophil Recruitment via JNK/c-JUN/AP-1 Signaling and Chromatin Modifications

Duox1-Derived H2O2 Modulates Cxcl8 Expression and Neutrophil Recruitment via JNK/c-JUN/AP-1 Signaling and Chromatin Modifications

Role of neutrophils in the activation of trypsinogen in severe acute pancreatitis

Retinal flavoprotein fluorescence correlates with mitochondrial stress, apoptosis, and chemokine expression

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