TY - JOUR
T1 - Mercury modulates interplay between IL-1, TNF-, and gap junctional intercellular communication in keratinocytes
T2 - Mitigation by lycopene
AU - Zefferino, Roberto
AU - Leone, Antonella
AU - Piccaluga, Simona
AU - Cincione, Raffaele
AU - Ambrosi, Luigi
PY - 2008/10
Y1 - 2008/10
N2 - Gap junctional intercellular communication (GJIC) is used to control cell proliferation. It is not surprising then that a lack of GJIC (i.e., during loss of contact inhibition among adjacent cells) is associated with cancer promotion/progression. There also seems to be a link between ineffective GJIC and increases in inflammatory events. Interestingly, many cytokines released during an inflammatory response also have critical roles in cancer cell survival. Specifically, TNF and IL-1 are important for initiating/augmenting CD8+- and NK-cell mediated killing; however, in what appears counterintuitive, eachat timescan act to protect cancer cells against apoptosis, a major mechanism for cell killing from within. It is thus plausible to assume that certain toxicants might act as cancer promoters in manners distinct from/augmentive of direct effects on DNA, i.e., by concurrently altering GJIC and cytokine formation in host or microenvironment of a cancer cell. Our research has evaluated effects of many toxicants upon keratinocytes; in particular, we have examined effects of mercury on GJIC and on TNF and IL-1 levels in (and secretion by) these cells. In the studies here, a tomato preparation (i.e., an oleoresin) bearing the antioxidant carotenoid lycopene was examined for its effects on GJIC and cytokine formation by keratinocytes in general, and its potential ability to mitigate/reverse the toxic effects of mercury in the cells in particular. It was shown that a 4-hr treatment with the oleoresin (containing 56, 6 nM lycopene) re-established GJIC amongand increased the formation of IL-1 and TNF that had been significantly reduced withinkeratinocytes that had been pre-treated for 24 hr with 10 nM HgCl2. These results show that effects of mercury likely depend on some level of oxidative stress and that its potential effects on keratinocyte GJIC and cytokine concentrations could, in an exposed host, be mitigated/reversed by increased dietary intake of carotenoids like lycopene.
AB - Gap junctional intercellular communication (GJIC) is used to control cell proliferation. It is not surprising then that a lack of GJIC (i.e., during loss of contact inhibition among adjacent cells) is associated with cancer promotion/progression. There also seems to be a link between ineffective GJIC and increases in inflammatory events. Interestingly, many cytokines released during an inflammatory response also have critical roles in cancer cell survival. Specifically, TNF and IL-1 are important for initiating/augmenting CD8+- and NK-cell mediated killing; however, in what appears counterintuitive, eachat timescan act to protect cancer cells against apoptosis, a major mechanism for cell killing from within. It is thus plausible to assume that certain toxicants might act as cancer promoters in manners distinct from/augmentive of direct effects on DNA, i.e., by concurrently altering GJIC and cytokine formation in host or microenvironment of a cancer cell. Our research has evaluated effects of many toxicants upon keratinocytes; in particular, we have examined effects of mercury on GJIC and on TNF and IL-1 levels in (and secretion by) these cells. In the studies here, a tomato preparation (i.e., an oleoresin) bearing the antioxidant carotenoid lycopene was examined for its effects on GJIC and cytokine formation by keratinocytes in general, and its potential ability to mitigate/reverse the toxic effects of mercury in the cells in particular. It was shown that a 4-hr treatment with the oleoresin (containing 56, 6 nM lycopene) re-established GJIC amongand increased the formation of IL-1 and TNF that had been significantly reduced withinkeratinocytes that had been pre-treated for 24 hr with 10 nM HgCl2. These results show that effects of mercury likely depend on some level of oxidative stress and that its potential effects on keratinocyte GJIC and cytokine concentrations could, in an exposed host, be mitigated/reversed by increased dietary intake of carotenoids like lycopene.
KW - Antioxidants
KW - Cancer
KW - Carotenoids
KW - Cytokines
UR - http://www.scopus.com/inward/record.url?scp=65249160572&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65249160572&partnerID=8YFLogxK
U2 - 10.1080/15476910802482854
DO - 10.1080/15476910802482854
M3 - Article
C2 - 19404869
AN - SCOPUS:65249160572
VL - 5
SP - 353
EP - 360
JO - Journal of Immunotoxicology
JF - Journal of Immunotoxicology
SN - 1547-691X
IS - 4
ER -