Signaling pathways involved in the physiological response of mussel hemocytes to bacterial challenge: the role of stress-activated p38 MAP kinases

Canesi, Laura; Betti, Michele; Ciacci, Caterina; Scarpato, Alfonso; Citterio, Barbara; Pruzzo, Carla; Gallo, Gabriella

doi:10.1016/s0145-305x(01)00078-7

Cited by 88 publications

(88 citation statements)

References 40 publications

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“…Accordingly, we have found p38-MAPK to exhibit a considerable and sustained phosphorylation profile in samples from gill tissue of mussels exposed to 30°C, while JNKs were shown to have a moderate and transient activation (Fig.1). The presence and activation of p38-MAPK and JNKs has been demonstrated before in mussel studies either in haemocytes during the immune response to a bacterial challenge (Canesi et al, 2002;Canesi et al, 2005) or in mantle and gill tissue from M. galloprovincialis species exposed to diverse forms of stress (Gaitanaki et al, 2004;Kefaloyianni et al, 2005). The sensitivity of gills to thermal stress could justify the more profound effect of hyperthermia on p38-MAPK phosphorylation compared with the kinase profile in mantle reported previously by our group (Kefaloyianni et al, 2005).…”

Section: Discussionsupporting

confidence: 69%

Hyperthermia-induced Hsp70 and MT20 transcriptional upregulation are mediated by p38-MAPK and JNKs inMytilus galloprovincialis(Lamarck); a pro-survival response

Gourgou

Aggeli

Beis

et al. 2010

Journal of Experimental Biology

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SUMMARYIn the present study we investigated the signal transduction cascades triggered by acute thermal stress in Mytilus galloprovincialis gills. This particular species has been reported to exhibit a significant tolerance to high temperatures; thus, it was intriguing to examine the molecular mechanisms responsible for this extraordinary trait. In particular, exposure to 30°C was found to cause a significant and sustained stimulation of p38-MAPK phosphorylation while the activation profile of JNKs was transient and relatively moderate. We also observed that hyperthermia induced apoptosis as a delayed response, with both MAPK subfamilies rapidly translocating to the nucleus. The phosphorylation of cJun, ATF2 and NFB was detected next. Using selective inhibitors, phosphorylation of these transcription factors was established to be dependent on p38-MAPK or JNKs. Subsequently, potential changes in gene expression were assessed. In this context, hyperthermia resulted in the transcriptional upregulation of Hsp70 and MT20 genes with a widely known salutary effect, preserving mussel fitness and performance under adverse environmental conditions. Interestingly, p38-MAPK and JNKs were found to mediate the hyperthermia-induced Hsp70 and MT20 upregulation as well as the delayed induction of apoptosis under the interventions studied. Overall this is, to our knowledge, the first time that an insight into the compensatory survival 'programme' initiated in Mytilus galloprovincialis gills, contributing to this organism's exceptional tolerance to thermal stress, has been gained. In particular, we provide evidence demonstrating the principal role of p38-MAPK and JNKs in transducing the stress signal via mobilization of specific transcription factors and the transcriptional upregulation of cytoprotective genes.

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Section: Discussionsupporting

confidence: 69%

Hyperthermia-induced Hsp70 and MT20 transcriptional upregulation are mediated by p38-MAPK and JNKs inMytilus galloprovincialis(Lamarck); a pro-survival response

Gourgou

Aggeli

Beis

et al. 2010

Journal of Experimental Biology

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“…1B). Neither inhibitor, at the concentration tested, showed cytotoxic effects in mussel hemocytes or affected lysosomal membrane stability (10,15) and phagocytosis (4) in control cells.…”

Section: Resultsmentioning

confidence: 99%

“…Hemolymph serum was obtained by centrifugation of whole hemolymph at 200 g for 10 min, and the supernatant was sterilized through a 0.22-m-pore filter. Hemocyte monolayers were prepared as previously described (10). Briefly, aliquots of 0.5 ml of hemolymph, corresponding to ϳ1-2 ϫ 10 6 cells, were seeded onto glass coverslips (40 ϫ 22 mm), placed in plastic culture dishes, and incubated at 16°C for 30 min to allow for cell attachment.…”

Section: Methodsmentioning

confidence: 99%

“…In experiments with antiestrogens, tamoxifen (100 nM final concentration, from a 10 mM stock solution in ethanol) was added 10 min before addition of E 2. In experiments with kinase inhibitors, before addition of E 2, hemocyte monolayers were pretreated for 20 min with 20 M SB-203580 (for p38 MAPK) or 2.5 M GF-109203X (for PKC) as previously described (10,15). For each experiment, control hemocyte samples were run in parallel.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Immunomodulation by 17β-estradiol in bivalve hemocytes

Canesi

Ciacci²,

Lorusso³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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.-In mammals, estrogens have dose-and cell-type-specific effects on immune cells and may act as pro-and anti-inflammatory stimuli, depending on the setting. In the bivalve mollusc Mytilus, the natural estrogen 17␤-estradiol (E2) has been shown to affect neuroimmune functions. We have investigated the immunomodulatory role of E 2 in Mytilus hemocytes, the cells responsible for the innate immune response. E2 at 5-25 nM rapidly stimulated phagocytosis and oxyradical production in vitro; higher concentrations of E 2 inhibited phagocytosis. E2-induced oxidative burst was prevented by the nitric oxide (NO) synthase inhibitor N G -monomethyl-L-arginine and superoxide dismutase, indicating involvement of NO and O 2 Ϫ ; NO production was confirmed by nitrite accumulation. The effects of E2 were prevented by the antiestrogen tamoxifen and by specific kinase inhibitors, indicating a receptor-mediated mechanism and involvement of p38 MAPK and PKC. E2 induced rapid and transient increases in the phosphorylation state of PKC, as well as of a aCREB-like (cAMP responsive element binding protein) transcription factor, as indicated by Western blot analysis with specific anti-phospho-antibodies. Localization of estrogen receptor-␣-and -␤-like proteins in hemocytes was investigated by immunofluorescence confocal microscopy. The effects of E2 on immune function were also investigated in vivo at 6 and 24 h in hemocytes of E2-injected mussels. E2 significantly affected hemocyte lysosomal membrane stability, phagocytosis, and extracellular release of hydrolytic enzymes: lower concentrations of E2 resulted in immunostimulation, and higher concentrations were inhibitory. Our data indicate that the physiological role of E2 in immunomodulation is conserved from invertebrates to mammals. estrogen; innate immunity; kinase-mediated cell signaling; Mytilus IN MAMMALS, ESTROGENS EXERT a broad spectrum of activities on a wide variety of cells and tissues, including the immune system. Estrogens have dose-and cell-type-specific effects on immune cells and may act as pro-and anti-inflammatory stimuli, depending on the setting (5,22,24,43). 17␤-Estradiol (E 2 ) can modulate the function of neutrophil granulocytes, monocytes, and macrophages; these cell types have been reported to express intracellular and membrane estrogen receptors (ERs), and their response to E 2 can be mediated by nuclear, classical or "genomic" pathways, as well as by rapid, "nongenomic" mechanisms of action (2,3,24,45). These latter mechanisms may be initiated at membrane or cytosolic locations (29,39,49) and can result in direct local effects (e.g., modification or ion fluxes) and regulation of gene transcription secondary to activation of cytosolic kinase cascades (5,22,24,29,43).Among invertebrates, estrogens have been identified in bivalve molluscs (25,34,40,43), in which their role has been mainly investigated in the control of gametogenesis (20,21,30,33,34). However, there is evidence that estrogen can represent an important signaling molecule that is involved in roles ot...

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“…7A, IFNc treatment induced a time dependent increase in phosphorylated ERK2, reaching a 2,5-fold increase at 30 min incubation (inset to Fig 7; P ≤ 0.05). The effect of IFNc on ERK2 phosphorylation was evaluated in hemocytes pre-treated with MAPK inhibitors (Canesi et al, 2002b). PD98059, a specific inhibitor of MEK, the upstream activator of MAPKs, prevented the IFNc-induced ERK2 phosphorylation, whereas SB203580, the inhibitor of the stress-activated p38 MAPK activation, only slightly reduced the response (Fig.…”

Section: Effect Of Ifnc On Mapk Phosphorylationmentioning

confidence: 99%

Tyrosine kinase‐mediated cell signalling in the activation of Mytilus hemocytes: possible role of STAT‐like proteins

Canesi

Betti

Ciacci

et al. 2003

Biology of the Cell

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In bivalve molluscs, cell-mediated immunity is carried out by circulating hemocytes, resembling the monocyte/macrophage lineage of vertebrates, that can kill the microbes through phagocytosis and various cytotoxic reactions. Previous data demonstrated that activation of MAPKs (Mitogen Activated Protein Kinases) is involved in the response of mussel hemocytes (Mytilus galloprovincialis Lam.) to bacterial challenge. In this work, the possibility that modulation of components of tyrosine kinase-mediated cell signalling may participate in the activation of mussel hemocytes was investigated. Cell pre-treatment with the macrophage activator IFNc significantly increased the bactericidal activity of mussel hemocytes towards E. coli. Human recombinant IFNc stimulated tyrosine phosphorylation of different members of STAT-like proteins (Signal Transducers and Activators of Transcription), as evaluated by Western blotting of hemocyte protein extracts with specific anti-phospho-STAT antibodies. A similar increase in phosphorylation of immunoreactive STATs was observed in hemocytes incubated with E. coli, this indicating that tyrosine phosphorylation of STAT-like members represents a physiological step in hemocyte activation. IFNc lead to persistent phosphorylation of immunoreactive STAT1, a transcription factor that plays a critical role in innate immunity towards Gram negative bacteria in mammalian systems; moreover, hemocyte pretreatment with IFNc significantly increased bacteria-induced STAT1 phosphorylation, whereas IFNa did not. IFNc also transiently affected the phosphorylation state of different MAPKs. The extent and time course of MAPK phosphorylation induced by IFNc were distinct from those elicited by either IFNa or bacterial challenge. Overall, the results indicate that the hemocyte function can be modulated by heterologous cytokines and bacterial signals that act in concert through tyrosine kinase-mediated transduction pathways converging on STAT-and MAPK-like members.

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Signaling pathways involved in the physiological response of mussel hemocytes to bacterial challenge: the role of stress-activated p38 MAP kinases

Cited by 88 publications

References 40 publications

Hyperthermia-induced Hsp70 and MT20 transcriptional upregulation are mediated by p38-MAPK and JNKs inMytilus galloprovincialis(Lamarck); a pro-survival response

Hyperthermia-induced Hsp70 and MT20 transcriptional upregulation are mediated by p38-MAPK and JNKs inMytilus galloprovincialis(Lamarck); a pro-survival response

Immunomodulation by 17β-estradiol in bivalve hemocytes

Tyrosine kinase‐mediated cell signalling in the activation of Mytilus hemocytes: possible role of STAT‐like proteins

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