Chitin modulates innate immune responses of keratinocytes.
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vor 13 Jahren
Chitin, after cellulose the second most abundant polysaccharide in
nature, is an essential component of exoskeletons of crabs, shrimps
and insects and protects these organisms from harsh conditions in
their environment. Unexpectedly, chitin has been found to activate
innate immune cells and to elicit murine airway inflammation. The
skin represents the outer barrier of the human host defense and is
in frequent contact with chitin-bearing organisms, such as
house-dust mites or flies. The effects of chitin on keratinocytes,
however, are poorly understood. We hypothesized that chitin
stimulates keratinocytes and thereby modulates the innate immune
response of the skin. Here we show that chitin is bioactive on
primary and immortalized keratinocytes by triggering production of
pro-inflammatory cytokines and chemokines. Chitin stimulation
further induced the expression of the Toll-like receptor (TLR) TLR4
on keratinocytes at mRNA and protein level. Chitin-induced effects
were mainly abrogated when TLR2 was blocked, suggesting that TLR2
senses chitin on keratinocytes. We speculate that chitin-bearing
organisms modulate the innate immune response towards pathogens by
upregulating secretion of cytokines and chemokines and expression
of MyD88-associated TLRs, two major components of innate immunity.
The clinical relevance of this mechanism remains to be defined.
nature, is an essential component of exoskeletons of crabs, shrimps
and insects and protects these organisms from harsh conditions in
their environment. Unexpectedly, chitin has been found to activate
innate immune cells and to elicit murine airway inflammation. The
skin represents the outer barrier of the human host defense and is
in frequent contact with chitin-bearing organisms, such as
house-dust mites or flies. The effects of chitin on keratinocytes,
however, are poorly understood. We hypothesized that chitin
stimulates keratinocytes and thereby modulates the innate immune
response of the skin. Here we show that chitin is bioactive on
primary and immortalized keratinocytes by triggering production of
pro-inflammatory cytokines and chemokines. Chitin stimulation
further induced the expression of the Toll-like receptor (TLR) TLR4
on keratinocytes at mRNA and protein level. Chitin-induced effects
were mainly abrogated when TLR2 was blocked, suggesting that TLR2
senses chitin on keratinocytes. We speculate that chitin-bearing
organisms modulate the innate immune response towards pathogens by
upregulating secretion of cytokines and chemokines and expression
of MyD88-associated TLRs, two major components of innate immunity.
The clinical relevance of this mechanism remains to be defined.
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