Search PubMed for publications by Dr Gene Mayer
Am J Physiol Regul Integr Comp Physiol. 2004 Feb; 286(2): R366-R372.
Davis JM, Murphy EA, Brown AS, Carmichael MD, Ghaffar A, Mayer EP.
Dept. of Exercise Science, 1300 Wheat St., Columbia, SC 29208. jmdavis@sc.edu
Both moderate exercise and the soluble oat fiber beta-glucan can increase immune
function and decrease risk of infection, but no information exists on their
possible combined effects. This study tested the effects of moderate exercise
and oat beta-glucan on respiratory infection, macrophage antiviral resistance,
and natural killer (NK) cell cytotoxicity. Mice were assigned to four groups:
exercise and water, exercise and oat beta-glucan, control water, or control oat
beta-glucan. Oat beta-glucan was fed in the drinking water for 10 days before
intranasal inoculation of herpes simplex virus type 1 (HSV-1) or euthanasia.
Exercise consisted of treadmill running (1 h/day) for 6 days. Macrophage
resistance to HSV-1 was increased with both exercise and oat beta-glucan,
whereas NK cell cytotoxicity was only increased with exercise. Exercise was also
associated with a 45 and 38% decrease in morbidity and mortality, respectively.
Mortality was also decreased with oat beta-glucan, but this effect did not reach
statistical significance. No additive effects of exercise and oat beta-glucan
were found. These data confirm a positive effect of both moderate exercise and
oat beta-glucan on immune function, but only moderate exercise was associated
with a significant reduction in the risk of upper respiratory tract infection in
this model.
Biochim Biophys Acta. 2003 Jun 17; 1641(1): 13-23.
Galectin-3 expression in macrophages is signaled by Ras/MAP
kinase pathway and up-regulated by modified lipoproteins.
Kim K, Mayer EP, Nachtigal M.
Department of Pathology and Microbiology, University of South Carolina-School of
Medicine, Columbia, SC 29208, USA.
To study the signaling pathway involved in the regulation of galectin-3
expression we used phorbol ester to stimulate macrophage differentiation of
THP-1 cells. Treatment with phorbol 12-myristate 13-acetate (PMA) increased
significantly the level of expression of galectin-3 in THP-1 cells. PMA-induced
galectin-3 overexpression was blocked by: protein kinase C inhibitors
staurosporine, calphostin C, and apigenin; tyrosine-specific protein kinase
inhibitors genistein and tyrphostin A25; PD 98059, a selective inhibitor of
mitogen-activated protein kinase (MAPK) kinase 1 (MEK1 or MKK1); and SB 203580,
a specific inhibitor of p38 MAPK. Galectin-3 up-regulation was not affected by
exposure to two inhibitors of cAMP-dependent protein kinase (PKA), H-89 and
KT5720. Co-transfection of pPG3.5, a plasmid vector containing the rabbit
galectin-3 promoter and the constructs pMCL-MKK1 N3 or pRC-RSV-MKK3Glu that
constitutively express MKK1 and MKK3, raised the activity of galectin-3 promoter
by 185% and 110%, respectively. Co-transfection with a Ha-Ras expression vector
stimulated galectin-3 promoter activity approximately 10-fold. Expression of
c-Jun or v-Jun raised the level of galectin-3 promoter activity more the three-
and fourfold, respectively. Co-transfection of c-Jun and pPG3.5 5'-upstream
deletion mutants resulted in a reduction of the galectin-3 promoter activity by
50% to 80%. Transfection of c-Jun, v-Jun or Ha-Ras increased significantly
galectin-3 protein in THP-1 cells. These findings indicated that Ras/MEKK1/MKK1-dependent/AP-1
signal transduction pathway plays an important role in the expression of
galectin-3 in PMA-stimulated macrophages. We further investigated the effect of
modified lipoproteins on galectin-3 expression in macrophages. Murine resident
peritoneal macrophages loaded with acetylated low-density lipoprotein (AcLDL) or
oxidized LDL (OxLDL) showed increased galectin-3 protein and mRNA. These results
showed that treatment of macrophages with PMA or modified lipoproteins results
in galectin-3 overexpression. These findings may explain the enhanced expression
of galectin-3 in atherosclerotic foam cells and suggest that Ras/MAPK signal
transduction pathway is involved in controlling this gene.
Int J Sports Med. 2001 May; 22(4): 261-7.
Tissue expression
and plasma concentrations of TNFalpha, IL-1beta, and IL-6 following treadmill
exercise in mice.
Colbert LH, Davis JM, Essig DA, Ghaffar A, Mayer EP.
Department of Exercise Science, School of Public Health, University of South
Carolina, Columbia, USA.
Exercise can increase plasma inflammatory cytokine concentrations in humans, but
tissue responses are not well studied. We examined plasma concentrations and
tissue expression of TNFalpha, IL-1beta, and IL-6 following treadmill running in
mice. C57B1/6 mice were randomly assigned to: non-exercise control (CON),
sacrifice at 0 or 1.5 h after 60 min running (MOD0, MOD 1.5), sacrifice at 0,
1.5, or 3 h after fatiguing running (approximately 3 h) (EX0, EX1.5, EX3), or
lipopolysaccharide (25 microg) with no exercise (LPS). Lung, liver, muscle, and
brain mRNA expression was analyzed (n = 4-6/group) using reverse
transcriptase-rapid polymerase chain reaction (RT-RPCR). Plasma cytokine
concentrations were determined (n =4-10/group) by ELISA. Plasma IL-6 was higher
in EX1.5, and lung TNFalpha mRNA was higher in EX1.5 and EX3 compared to CON (P
< 0.05). No significant increases in plasma cytokine concentrations or tissue
cytokine expression were found in other EX groups. LPS significantly increased
these cytokine measures in tissues and plasma, with the exception of plasma
IL-1beta which was undetectable. The source of the plasma IL-6 following
exercise does not appear to be lung, liver, muscle, or brain tissue, and remains
to be determined. These data also suggest that tissue level cytokine expression
may not necessarily lead to increased plasma cytokine concentrations.
J Leukoc Biol. 2001 Apr; 69(4): 575-82.
The collagenous domain of class A scavenger receptors is
involved in macrophage adhesion to collagens.
Gowen BB, Borg TK, Ghaffar A, Mayer EP.
Department of Microbiology and Immunology, University of South Carolina, School
of Medicine, Columbia 29208, USA.
Class A macrophage scavenger receptors (MSRs) have a remarkably broad ligand
specificity and are well-known for their roles in atherogenesis and host
defense. Recently, we demonstrated that these receptors also recognize and
mediate adhesion to denatured forms of type I collagen. In this study, the
involvement of the collagenous domain of MSRs in binding to denatured type I
collagen was investigated. Transient expression of full-length, native type II
MSR in COS-1 cells conferred adhesion to denatured type I collagens, whereas
expression of a truncated receptor lacking the distal portion of the collagenous
domain did not. Further, a synthetic peptide derived from the collagenous domain
was effective in abrogating Mphi adhesion to denatured forms of type I collagen.
We also addressed collagen-type specificity by examining MSR affinity for type
III and type IV collagens. As with type I collagen, Mphis adhered only to
denatured forms of type III collagen. Moreover, the adhesion was mediated by
MSRs. In contrast, adhesion to denatured type IV collagen was not shown to be
MSR-dependent, but adhesion to the native form was. MSR-mediated adhesion to
types III and IV collagens was also shown to be dependent on the collagenous
domain. Taken together, these data strongly suggest that the collagenous domain
is involved in MSR-mediated adhesion to denatured forms of types I and III
collagens and native, but not denatured, type IV collagen.
Med Sci Sports Exerc. 2000 Oct; 32(10): 1704-8.
Exercise and tumor development in a mouse predisposed to
multiple intestinal adenomas.
Colbert LH, Davis JM, Essig DA, Ghaffar A, Mayer EP.
Department of Exercise Science, School of Public Health, University of South
Carolina, Columbia 29208, USA.
Epidemiological evidence suggests that physical activity may be protective
against the development of colon cancer. Potential mechanisms remain largely
unexplored due to the paucity of appropriate experimental models. PURPOSE: The
purpose of this study was to examine the effect of exercise training on polyp
development in an induced mutant mouse strain predisposed to multiple intestinal
neoplasia (Min mouse). METHODS: Three-week-old male and female heterozygotes
were randomly assigned to control (CON; 10 males, 6 females) or exercise (EX; 11
males, 11 females) groups. In the first week, EX mice were acclimated to
treadmill running at 10-18 m x min(-1) for 15-60 min x d(-1). From 4-10 wk of
age, mice ran at 18-21 m x min(-1) for 60 min. CON mice sat in Plexiglas lanes
suspended above the treadmill for the same time periods. At 10 wk of age, the
mice were sacrificed and the intestines removed, opened, and counted for polyps.
RESULTS: Skeletal muscle oxidative capacity increased with training as shown by
a 64% increase in citrate synthase activity in the gastrocnemius/soleus muscle
of EX compared with CON (P = 0.009). There were no significant effects of
exercise in the males and females combined on small intestine, colon, or total
intestinal polyps (P > 0.05). When analyzed separately, however, there were
fewer colon and total polyps in the EX than in the CON males, although the
difference was not statistically significant (P = 0.06). CONCLUSIONS: These
results suggest that seven weeks of exercise training do not affect the
development of intestinal polyps in the Min mouse. Further studies are required
to determine if a true sex difference exists or if variations on the current
training protocol may affect tumor outcomes.
Matrix Biol. 2000 Feb; 19(1): 61-71.
Selective adhesion of macrophages to denatured forms of type
I collagen is mediated by scavenger receptors.
Gowen BB, Borg TK, Ghaffar A, Mayer EP.
Department of Microbiology and Immunology, University of South Carolina, School
of Medicine, Columbia 29208, USA.
Macrophages (Mφs) are multifunctional immune cells which are involved in the
regulation of immune and inflammatory responses, as well as in tissue repair and
remodeling. In tissues, Mφs reside in areas which are rich in extracellular
matrix (ECM), the structural component which also plays an essential role in
regulating a variety of cellular functions. A major ECM protein encountered by
Mφs is type I collagen, the most abundant of the fibril-forming collagens.
In this study, the adhesion of RAW 264.7 murine Mphis to native fibrillar,
monomeric, and denatured type I collagen was investigated. Using atomic force
microscopy, structural differences between fibrillar and monomeric type I
collagen were clearly resolved. When cultured on fibrillar type I collagen,
Mphis adhered poorly. In contrast, they adhered significantly to monomeric,
heat-denatured, or collagenase-modified type I collagen. Studies utilizing
anti-beta1 and -beta2 integrin adhesion-blocking antibodies, RGD-containing
peptides, or divalent cation-free conditions did not inhibit Mphi; adhesion to
monomeric or denatured type I collagen. However, macrophage scavenger receptor (MSR)
ligands and anti-MSR antibodies significantly blocked Mphi; adhesion to
denatured and monomeric type I collagen strongly suggesting the involvement of
the MSR as an adhesion molecule for denatured type I collagen. Further analysis
by Western blot identified the MSR as the primary receptor for denatured type I
collagen among Mphi; proteins purified from a heat-denatured type I collagen
affinity column. These findings indicate that Mphis adhere selectively to
denatured forms of type I collagen, but not the native fibrillar conformation,
via their scavenger receptors.
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