Biomedical Engineering Reference
In-Depth Information
h e phosphorylation of IκB is a key regulatory step in the activation of NF-κB.
Spiecker
et al.
(1997) determined how NO inhibits NF-κB and examined the fate of
IκBα following tumor necrosis factor (TNF)-α stimulation in the presence of NO
donors. h ey found that activation of NF-κB by TNF-α occurred within a short
period of time and coincided with the rapid degradation of IκBα. Co-treatment with
NO donors did not prevent IκBα degradation. However, NO donors inhibited NF-
κB activation and augmented IκBα resynthesis and nuclear translocation at er 2 hr
of TNF-α stimulation. h is correlated with a reduction in TNF-α-induced VCAM-1
expression. h ey also used murine macrophage-like RAW 264.7cells, co-cultured
with ECs to examine the ef ects of endogenously derived NO on cell adhesion
molecule expression. h e results showed that induction of RAW 264.7-derived NO
inhibited lipopolysaccharide-induced endothelial VCAM-1 expression, which was
reversed by the addition of the NOS inhibitor, L-NMMA. h ose i ndings indicate
that NO inhibits NF-κB activation and VCAM-1 expression by increasing the
expression and nuclear translocation of IκBα. A study by Nolan
et al.
(2008) used
a simplii ed in vitro system to identify the mechanism for regulating neutrophil
migration by NO. h ey found that inhibition of constitutive NO production may
lead to increased neutrophil migration through microparticle formation and thus
propagation of the inl ammatory response. Microparticles are formed from the
membrane of activated immune cells and express adhesion molecules that enable
them to inl uence cell-cell interactions and cell recruitment. Neutrophil-derived
microparticles have been shown to contain inl ammatory mediators such as platelet-
activating factor, CD11a, CD11b, L-selectin, and P-selectin glycoprotein ligand 1
(PSGL-1) and to activate ECs causing the release of pro-inl ammatory cytokines.
In that study, they found that regulation of adhesion by NO may involve direct
ef ects on leukocytes. Pretreatment of microparticles with antibodies to L-selectin
and PSGL-1 signii cantly inhibited neutrophil migration. h e ability of L-NAME-
induced microparticles to enhance migration was found to be dependent on the
number of microparticles produced. h ose data showed that NO can modulate
neutrophil migration by regulating microparticle formation.
SUMMARY
• Arg plays important roles in maintaining health and immunity.
• h e inl uences of Arg on modulating immune response may mainly
depend on NO.
• Most studies have suggested that Arg or NO administration reduces
adhesion molecule expression and decreases leukocyte adherence and
transmigrations.
• Some conl icting results showed that the use of Arg or NO enhances
adhesion molecule expression and thus aggravates inl ammatory reaction.
