2.1.4 The TOLL receptor
Toll-like receptor (TLR) is a molecular pattern associated with the
recognition of specific pathogens. Toll-like receptor-2 recognizes
multiple microbial components of Gram-positive bacteria and TLR4 is
required for the lipopolysaccharide response, an external component of
Gram-negative bacterial membranes52.TLR4 activation
has been associated with neonatal lung
inflammation53,54. Studies showed that caffeine had no
significant effect on TLR2 and 4 in normal neonatal rat lung tissue, but
increased TLR9 expression, limited TLR4 expansion, inhibited
pro-inflammatory cytokine production, and reduced the severity of
BPD55. In addition, Ren et al.found that caffeine may
inhibit the TLR-mediated inflammatory cascade response in macrophages by
suppressing calcium mobilization56. It was also
demonstrated in human monocytes that high concentrations of caffeine
(200µM) upregulated TLR4 to promote inflammation, while 50 and 100µM of
caffeine downregulated TLR1 and TLR2 expression and was able to reduce
TNF-α levels;this may be related to the reduced incidence of BPD by
caffeine57.